FAM227B

Chr 15

family with sequence similarity 227 member B

Also known as: C15orf33

NCBI Gene: 196951 ENSG00000166262 UniProt: Q96M60

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.43

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score -0.36

OE 1.07 (0.81–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.07Z-score

OE missense 0.99 (0.89–1.10)

245 obs / 248.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.07 (0.81–1.43)

0≤0.351.4

Missense OE?0.99 (0.89–1.10)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 33 / 30.8Missense obs/exp: 245 / 248.2Syn Z: -0.32

Background carrier burden — how many people carry a rare variant somewhere in FAM227B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 74

715 rare PASS variants

Rare truncating (LoF)

1 in 190

195 rare PASS variants

Rare synonymous (reference)

1 in 190

233 rare PASS variants

Rare missense and truncating variants are carried at similar rates in FAM227B; this gene does not show strong loss-of-function constraint by this measure. 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 170
South Asian	~43k	1 in 100	1 in 290
Remaining (unassigned)	~30k	1 in 75	1 in 240
European (Finnish)	~27k	1 in 270	1 in 430
Admixed American	~22k	1 in 70	1 in 160
African / African American	~21k	1 in 78	1 in 450
East Asian	~20k	1 in 85	1 in 330
Ashkenazi Jewish	~13k	1 in 910	1 in 920
Middle Eastern	~2,884	1 in 61	1 in 150

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 15 coding exons well covered in gnomAD exomes; exons 3, 4, 5, 6, 8 and 3 more marginal. Genomes: all 15.? see exons ↓