chr3-130405426-A-G

Variant names:

• chr3-130405426-A-G
• rs1497313
• NM_001278298.2:c.4282-162A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278298.2(COL6A5):​c.4282-162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,068 control chromosomes in the GnomAD database, including 40,644 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 0.72 (40644 hom., cov: 31)
• Consequence: COL6A5 NM_001278298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A5	NM_001278298.2	c.4282-162A>G		intron_variant	Intron 13 of 40	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7	c.4282-162A>G		intron_variant	Intron 13 of 39		NP_694996.5
COL6A5	NR_022012.3	n.4620-162A>G		intron_variant	Intron 13 of 41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A5	ENST00000373157.9	c.4282-162A>G		intron_variant	Intron 13 of 40	2	NM_001278298.2	ENSP00000362250.5
COL6A5	ENST00000312481.11	n.4282-162A>G		intron_variant	Intron 13 of 41	1		ENSP00000309762.7
COL6A5	ENST00000512836.6	c.4282-162A>G		intron_variant	Intron 13 of 39	2		ENSP00000422898.2

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110198 AN: 151950 Hom.: 40631 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.723

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.725 AC: 110245 AN: 152068 Hom.: 40644 Cov.: 31 AF XY: 0.725 AC XY: 53905 AN XY: 74328

African (AFR) AF: 0.626 AC: 25944 AN: 41458

American (AMR) AF: 0.714 AC: 10908 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2529 AN: 3470

East Asian (EAS) AF: 0.524 AC: 2697 AN: 5146

South Asian (SAS) AF: 0.601 AC: 2889 AN: 4806

European-Finnish (FIN) AF: 0.881 AC: 9324 AN: 10586

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53492 AN: 68004

Other (OTH) AF: 0.721 AC: 1521 AN: 2110

Alfa AF: 0.726 Hom.: 4196

Bravo AF: 0.706

Asia WGS AF: 0.569 AC: 1978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.023
DANN	Benign	0.64
PhyloP100		-2.0
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: rs1497313; hg19: chr3-130124270; COSMIC: COSV55213685;