NM_001278298.2:c.4761+645T>C

Variant names:

• chr3-130414776-T-C
• rs1497309
• NM_001278298.2:c.4761+645T>C

Variant summary

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

The NM_001278298.2(COL6A5):​c.4761+645T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,906 control chromosomes in the GnomAD database, including 28,826 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 0.59 (28826 hom., cov: 31)
• Consequence: COL6A5 NM_001278298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• Publications: 3 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=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A5	NM_001278298.2	c.4761+645T>C		intron_variant	Intron 22 of 40	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7	c.4761+645T>C		intron_variant	Intron 22 of 39		NP_694996.5
COL6A5	NR_022012.3	n.5099+645T>C		intron_variant	Intron 22 of 41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A5	ENST00000373157.9	c.4761+645T>C		intron_variant	Intron 22 of 40	2	NM_001278298.2	ENSP00000362250.5
COL6A5	ENST00000312481.11	n.4761+645T>C		intron_variant	Intron 22 of 41	1		ENSP00000309762.7
COL6A5	ENST00000512836.6	c.4761+645T>C		intron_variant	Intron 22 of 39	2		ENSP00000422898.2

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89701 AN: 151788 Hom.: 28826 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.591 AC: 89725 AN: 151906 Hom.: 28826 Cov.: 31 AF XY: 0.587 AC XY: 43559 AN XY: 74232

African (AFR) AF: 0.385 AC: 15931 AN: 41420

American (AMR) AF: 0.551 AC: 8403 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2330 AN: 3472

East Asian (EAS) AF: 0.186 AC: 959 AN: 5156

South Asian (SAS) AF: 0.461 AC: 2216 AN: 4810

European-Finnish (FIN) AF: 0.780 AC: 8248 AN: 10568

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49533 AN: 67922

Other (OTH) AF: 0.595 AC: 1257 AN: 2112

Alfa AF: 0.680 Hom.: 18520

Bravo AF: 0.562

Asia WGS AF: 0.329 AC: 1145 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.0
DANN	Benign	0.88
PhyloP100		0.14
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: rs1497309; hg19: chr3-130133620;