rs1542829

Variant names:

• chr3-130418627-G-A
• rs1542829
• NM_001278298.2:c.4888-242G>A

Variant summary

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

The NM_001278298.2(COL6A5):​c.4888-242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 152,042 control chromosomes in the GnomAD database, including 614 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 0.082 (614 hom., cov: 31)
• Consequence: COL6A5 NM_001278298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A5	NM_001278298.2	c.4888-242G>A		intron_variant	Intron 24 of 40	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7	c.4888-242G>A		intron_variant	Intron 24 of 39		NP_694996.5
COL6A5	NR_022012.3	n.5226-242G>A		intron_variant	Intron 24 of 41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A5	ENST00000373157.9	c.4888-242G>A		intron_variant	Intron 24 of 40	2	NM_001278298.2	ENSP00000362250.5
COL6A5	ENST00000312481.11	n.4888-242G>A		intron_variant	Intron 24 of 41	1		ENSP00000309762.7
COL6A5	ENST00000512836.6	c.4888-242G>A		intron_variant	Intron 24 of 39	2		ENSP00000422898.2

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12489 AN: 151924 Hom.: 613 Cov.: 31

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0640

Gnomad OTH AF: 0.0872

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

GnomAD4 genome AF: 0.0823 AC: 12511 AN: 152042 Hom.: 614 Cov.: 31 AF XY: 0.0839 AC XY: 6235 AN XY: 74328

African (AFR) AF: 0.0916 AC: 3797 AN: 41472

American (AMR) AF: 0.119 AC: 1821 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0701 AC: 243 AN: 3468

East Asian (EAS) AF: 0.175 AC: 902 AN: 5156

South Asian (SAS) AF: 0.157 AC: 755 AN: 4814

European-Finnish (FIN) AF: 0.0339 AC: 359 AN: 10586

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0640 AC: 4347 AN: 67968

Other (OTH) AF: 0.0892 AC: 188 AN: 2108

Alfa AF: 0.0738 Hom.: 2079

Bravo AF: 0.0894

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.44
PhyloP100		-0.30
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: rs1542829; hg19: chr3-130137471; COSMIC: COSV107198827;