rs781038607

chr21-45990404-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001848.3(COL6A1):c.984C>T(p.Asp328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,091,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: COL6A1 NM_001848.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.212

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 21-45990404-C-T is Benign according to our data. Variant chr21-45990404-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 476444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.212 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3	c.984C>T	p.Asp328=	synonymous_variant	13/35	ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8	c.984C>T	p.Asp328=	synonymous_variant	13/35	1	NM_001848.3	P1

Frequencies

GnomAD3 genomes AF: 0.000716 AC: 17 AN: 23736 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.00151

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00139

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00105

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000543 AC: 11 AN: 202546 Hom.: 0 AF XY: 0.0000536 AC XY: 6 AN XY: 111852

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000114

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000238 AC: 254 AN: 1067332 Hom.: 0 Cov.: 49 AF XY: 0.000266 AC XY: 139 AN XY: 522642

Gnomad4 AFR exome AF: 0.000134

Gnomad4 AMR exome AF: 0.0000335

Gnomad4 ASJ exome AF: 0.0000723

Gnomad4 EAS exome AF: 0.000487

Gnomad4 SAS exome AF: 0.0000383

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000273

Gnomad4 OTH exome AF: 0.000108

GnomAD4 genome AF: 0.000716 AC: 17 AN: 23736 Hom.: 0 Cov.: 0 AF XY: 0.000796 AC XY: 9 AN XY: 11306

Gnomad4 AFR AF: 0.000170

Gnomad4 AMR AF: 0.000525

Gnomad4 ASJ AF: 0.00151

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00139

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00105

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000329 Hom.: 0

Bravo AF: 0.000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

COL6A1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 27, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Bethlem myopathy 1A Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	3.9
Dann	Benign	0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs781038607; hg19: chr21-47410318; COSMIC: COSV62611401; COSMIC: COSV62611401;