rs117470181

Positions:

• chr21-45986722-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001848.3(COL6A1):​c.588+37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,538,340 control chromosomes in the GnomAD database, including 1,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (94 hom., cov: 33)
  • Exomes 𝑓: 0.013 (1061 hom.)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.370

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 21-45986722-A-G is Benign according to our data. Variant chr21-45986722-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 93881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45986722-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3	c.588+37A>G		intron_variant		ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8	c.588+37A>G		intron_variant		1	NM_001848.3	P1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1672 AN: 151434 Hom.: 94 Cov.: 33

Gnomad AFR AF: 0.00110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00693

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.00274

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00328

Gnomad OTH AF: 0.00817

GnomAD3 exomes AF: 0.0276 AC: 4063 AN: 147114 Hom.: 223 AF XY: 0.0310 AC XY: 2428 AN XY: 78346

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.00570

Gnomad EAS exome AF: 0.136

Gnomad SAS exome AF: 0.0819

Gnomad FIN exome AF: 0.00333

Gnomad NFE exome AF: 0.00349

Gnomad OTH exome AF: 0.0179

GnomAD4 exome AF: 0.0128 AC: 17721 AN: 1386788 Hom.: 1061 Cov.: 35 AF XY: 0.0148 AC XY: 10108 AN XY: 684298

Gnomad4 AFR exome AF: 0.000826

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.00633

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.0816

Gnomad4 FIN exome AF: 0.00352

Gnomad4 NFE exome AF: 0.00260

Gnomad4 OTH exome AF: 0.0153

GnomAD4 genome AF: 0.0110 AC: 1674 AN: 151552 Hom.: 94 Cov.: 33 AF XY: 0.0133 AC XY: 985 AN XY: 74044

Gnomad4 AFR AF: 0.00109

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.00693

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0832

Gnomad4 FIN AF: 0.00274

Gnomad4 NFE AF: 0.00328

Gnomad4 OTH AF: 0.00760

Alfa AF: 0.00578 Hom.: 4

Bravo AF: 0.0108

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 05, 2012	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.91
DANN	Benign	0.37

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: rs117470181; hg19: chr21-47406636;