3-130413358-C-T

Variant names:

• chr3-130413358-C-T
• rs16827446
• NM_001278298.2:c.4663-187C>T

Variant summary

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

The NM_001278298.2(COL6A5):​c.4663-187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 151,746 control chromosomes in the GnomAD database, including 791 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 0.084 (791 hom., cov: 32)
• Consequence: COL6A5 NM_001278298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A5	NM_001278298.2	c.4663-187C>T		intron_variant	Intron 20 of 40	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7	c.4663-187C>T		intron_variant	Intron 20 of 39		NP_694996.5
COL6A5	NR_022012.3	n.5001-187C>T		intron_variant	Intron 20 of 41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A5	ENST00000373157.9	c.4663-187C>T		intron_variant	Intron 20 of 40	2	NM_001278298.2	ENSP00000362250.5
COL6A5	ENST00000312481.11	n.4663-187C>T		intron_variant	Intron 20 of 41	1		ENSP00000309762.7
COL6A5	ENST00000512836.6	c.4663-187C>T		intron_variant	Intron 20 of 39	2		ENSP00000422898.2

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12728 AN: 151628 Hom.: 789 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.0934

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

GnomAD4 genome AF: 0.0840 AC: 12751 AN: 151746 Hom.: 791 Cov.: 32 AF XY: 0.0818 AC XY: 6064 AN XY: 74124

African (AFR) AF: 0.0862 AC: 3575 AN: 41460

American (AMR) AF: 0.0883 AC: 1346 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3468

East Asian (EAS) AF: 0.0911 AC: 469 AN: 5146

South Asian (SAS) AF: 0.0557 AC: 267 AN: 4790

European-Finnish (FIN) AF: 0.0405 AC: 427 AN: 10556

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0867 AC: 5874 AN: 67778

Other (OTH) AF: 0.0925 AC: 194 AN: 2098

Alfa AF: 0.0888 Hom.: 406

Bravo AF: 0.0896

Asia WGS AF: 0.0690 AC: 241 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.35
PhyloP100		1.5
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: rs16827446; hg19: chr3-130132202;