rs4688761

Variant names:

• chr3-130406145-C-T
• rs4688761
• NM_001278298.2:c.4395C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001278298.2(COL6A5):​c.4395C>T​(p.Asp1465Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,547,310 control chromosomes in the GnomAD database, including 362,653 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (28131 hom., cov: 32)
  • Exomes 𝑓: 0.68 (334522 hom.)
• Consequence: COL6A5 NM_001278298.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.23
• Publications: 17 publications found

Genes affected

COL6A5 (HGNC:26674): (collagen type VI alpha 5 chain) 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-7.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A5	NM_001278298.2	c.4395C>T	p.Asp1465Asp	synonymous_variant	Exon 16 of 41	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7	c.4395C>T	p.Asp1465Asp	synonymous_variant	Exon 16 of 40		NP_694996.5
COL6A5	NR_022012.3	n.4733C>T		non_coding_transcript_exon_variant	Exon 16 of 42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A5	ENST00000373157.9	c.4395C>T	p.Asp1465Asp	synonymous_variant	Exon 16 of 41	2	NM_001278298.2	ENSP00000362250.5
COL6A5	ENST00000312481.11	n.4395C>T		non_coding_transcript_exon_variant	Exon 16 of 42	1		ENSP00000309762.7
COL6A5	ENST00000512836.6	c.4395C>T	p.Asp1465Asp	synonymous_variant	Exon 16 of 40	2		ENSP00000422898.2

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87895 AN: 151926 Hom.: 28131 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.593

GnomAD2 exomes AF: 0.591 AC: 90933 AN: 153976 AF XY: 0.592

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.494

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.171

Gnomad FIN exome AF: 0.775

Gnomad NFE exome AF: 0.723

Gnomad OTH exome AF: 0.628

GnomAD4 exome AF: 0.680 AC: 949084 AN: 1395264 Hom.: 334522 Cov.: 38 AF XY: 0.677 AC XY: 465912 AN XY: 688312

African (AFR) AF: 0.335 AC: 10564 AN: 31518

American (AMR) AF: 0.494 AC: 17652 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 16969 AN: 25152

East Asian (EAS) AF: 0.164 AC: 5869 AN: 35714

South Asian (SAS) AF: 0.482 AC: 38172 AN: 79130

European-Finnish (FIN) AF: 0.769 AC: 37896 AN: 49276

Middle Eastern (MID) AF: 0.628 AC: 3568 AN: 5686

European-Non Finnish (NFE) AF: 0.727 AC: 781809 AN: 1075216

Other (OTH) AF: 0.632 AC: 36585 AN: 57874

GnomAD4 genome AF: 0.578 AC: 87911 AN: 152046 Hom.: 28131 Cov.: 32 AF XY: 0.575 AC XY: 42763 AN XY: 74320

African (AFR) AF: 0.344 AC: 14244 AN: 41422

American (AMR) AF: 0.548 AC: 8365 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2306 AN: 3472

East Asian (EAS) AF: 0.183 AC: 948 AN: 5176

South Asian (SAS) AF: 0.460 AC: 2215 AN: 4812

European-Finnish (FIN) AF: 0.780 AC: 8255 AN: 10578

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.728 AC: 49501 AN: 67998

Other (OTH) AF: 0.585 AC: 1234 AN: 2108

Alfa AF: 0.653 Hom.: 29447

Bravo AF: 0.548

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.050
DANN	Benign	0.32
PhyloP100		-7.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4688761; hg19: chr3-130124989; COSMIC: COSV55196280;