SMARCC1

Chr 3

SWI/SNF related BAF chromatin remodeling complex subunit C1

Also known as: BAF155, CRACC1, HYC5, Rsc8, SRG3, SWI3

NCBI Gene: 6599 ENSG00000173473 UniProt: Q92922

SMARCC1 encodes a component of SWI/SNF chromatin remodeling complexes that alters chromatin structure in an ATP-dependent manner and is essential for neural stem cell proliferation and neuronal differentiation. Mutations cause autosomal dominant congenital hydrocephalus with susceptibility to this condition. The gene is highly constrained against loss-of-function variants (pLI >0.99), reflecting its critical role in neurodevelopment.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and contains a predicted leucine zipper motif typical of many transcription factors. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHydrocephalus, congenital, 5

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · SMARCC1-associated developmental dysgenesis syndrome · AD · ClinGen 2023

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.12

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — SMARCC1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 7.23

OE 0.04 (0.02–0.12)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.45Z-score

OE missense 0.72 (0.67–0.78)

438 obs / 607.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.04 (0.02–0.12)

0≤0.351.4

Missense OE?0.72 (0.67–0.78)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 3 / 66.7Missense obs/exp: 438 / 607.7Syn Z: 0.24

Background carrier burden — how many people carry a rare variant somewhere in SMARCC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 62

1,222 rare PASS variants

Rare truncating (LoF)

1 in 3,100

98 rare PASS variants

Rare synonymous (reference)

1 in 110

540 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SMARCC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 2,700
South Asian	~43k	1 in 59	1 in 3,600
Remaining (unassigned)	~30k	1 in 56	≈ 1 in 7,400
European (Finnish)	~27k	1 in 130	≈ 1 in 26,000
Admixed American	~22k	1 in 64	1 in 1,300
African / African American	~21k	1 in 56	≈ 1 in 4,300
East Asian	~20k	1 in 64	≈ 1 in 4,600
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 6,000
Middle Eastern	~2,884	1 in 110	≈ 1 in 2,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 19 of 28 coding exons well covered in gnomAD exomes; exons 3, 4, 5, 8, 12 and 4 more marginal. Genomes: all 28.? see exons ↓