rs4688761

Positions:

• chr3-130406145-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001278298.2(COL6A5):​c.4395C>T​(p.Asp1465=) 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
COL6A5	NM_001278298.2	c.4395C>T	p.Asp1465=	synonymous_variant	16/41	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7	c.4395C>T	p.Asp1465=	synonymous_variant	16/40		NP_694996.5
COL6A5	NR_022012.3	n.4733C>T		non_coding_transcript_exon_variant	16/42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A5	ENST00000373157.9	c.4395C>T	p.Asp1465=	synonymous_variant	16/41	2	NM_001278298.2	ENSP00000362250	P2
COL6A5	ENST00000312481.11	c.4395C>T	p.Asp1465=	synonymous_variant, NMD_transcript_variant	16/42	1		ENSP00000309762
COL6A5	ENST00000512836.6	c.4395C>T	p.Asp1465=	synonymous_variant	16/40	2		ENSP00000422898	A2

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

GnomAD3 exomes AF: 0.591 AC: 90933 AN: 153976 Hom.: 29389 AF XY: 0.592 AC XY: 48345 AN XY: 81696

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 SAS exome AF: 0.479

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

Gnomad4 AFR exome AF: 0.335

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.675

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.769

Gnomad4 NFE exome AF: 0.727

Gnomad4 OTH exome AF: 0.632

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

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.585

Alfa AF: 0.654 Hom.: 22042

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

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