COL6A5

Chr 3

collagen type VI alpha 5 chain

Also known as: COL29A1, VWA4

NCBI Gene: 256076 ENSG00000172752 UniProt: A8TX70 OMIM: 611916

This gene encodes a member of the collagen superfamily of proteins. The encoded protein contains multiple von Willebrand factor A-like domains and may interact with the alpha 1 and alpha 2 chains of collagen VI to form the complete collagen VI trimer. Polymorphisms in this gene may be linked to dermal phenotypes, such as eczema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.92

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.92LOEUF

pLI 0.000

Z-score 2.25

OE 0.77 (0.64–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.18Z-score

OE missense 0.83 (0.79–0.87)

1093 obs / 1315.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.77 (0.64–0.92)

0≤0.351.4

Missense OE?0.83 (0.79–0.87)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 83 / 108.3Missense obs/exp: 1093 / 1315.7Syn Z: 2.94

Background carrier burden — how many people carry a rare variant somewhere in COL6A5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 16

3,219 rare PASS variants

Rare truncating (LoF)

1 in 140

497 rare PASS variants

Rare synonymous (reference)

1 in 33

1,105 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COL6A5. 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 23	1 in 220
South Asian	~43k	1 in 13	1 in 110
Remaining (unassigned)	~30k	1 in 12	1 in 67
European (Finnish)	~27k	1 in 55	1 in 390
Admixed American	~22k	1 in 15	1 in 110
African / African American	~21k	1 in 13	1 in 110
East Asian	~20k	1 in 19	1 in 150
Ashkenazi Jewish	~13k	1 in 71	1 in 640
Middle Eastern	~2,884	1 in 14	1 in 110

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): 33 of 40 coding exons well covered in gnomAD exomes; exons 2, 10, 14, 19, 24 and 2 more marginal. Genomes: all 40.? see exons ↓