rs2742071

chr21-45993171-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001848.3(COL6A1):c.1335+361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,324 control chromosomes in the GnomAD database, including 1,326 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 0.13 (1326 hom., cov: 34)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

Genes affected

COL6A1 (HGNC:2211): (collagen type VI alpha 1 chain) The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix proteins and have a triple-helical domain as their common structural element. Collagen VI is a major structural component of microfibrils. The basic structural unit of collagen VI is a heterotrimer of the alpha1(VI), alpha2(VI), and alpha3(VI) chains. The alpha2(VI) and alpha3(VI) chains are encoded by the COL6A2 and COL6A3 genes, respectively. The protein encoded by this gene is the alpha 1 subunit of type VI collagen (alpha1(VI) chain). Mutations in the genes that code for the collagen VI subunits result in the autosomal dominant disorder, Bethlem myopathy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3	c.1335+361C>T		intron_variant		ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8	c.1335+361C>T		intron_variant		1	NM_001848.3	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20019 AN: 152206 Hom.: 1327 Cov.: 34

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0729

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.131 AC: 20024 AN: 152324 Hom.: 1326 Cov.: 34 AF XY: 0.130 AC XY: 9716 AN XY: 74484

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0832

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0723

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.121

Alfa AF: 0.131 Hom.: 173

Bravo AF: 0.127

Asia WGS AF: 0.107 AC: 374 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	3.2
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2742071; hg19: chr21-47413085;