rs1053315

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000361866.8(COL6A1):c.2667G>A(p.Ala889=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,612,626 control chromosomes in the GnomAD database, including 75,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8043 hom., cov: 35)

Exomes 𝑓: 0.30 ( 67749 hom. )

Consequence

COL6A1
ENST00000361866.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -1.28

Variant links:

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]

COL6A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 21-46003593-G-A is Benign according to our data. Variant chr21-46003593-G-A is described in ClinVar as [Benign]. Clinvar id is 93864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46003593-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A1	NM_001848.3 linkuse as main transcript	c.2667G>A	p.Ala889=	synonymous_variant	35/35	ENST00000361866.8	NP_001839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8 linkuse as main transcript	c.2667G>A	p.Ala889=	synonymous_variant	35/35	1	NM_001848.3	ENSP00000355180	P1

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48515

AN:

152068

Hom.:

8036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.296

GnomAD3 exomes

AF:

0.282

AC:

69549

AN:

246606

Hom.:

10317

AF XY:

0.277

AC XY:

37267

AN XY:

134398

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.148

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.305

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.301

AC:

440268

AN:

1460440

Hom.:

67749

Cov.:

AF XY:

0.298

AC XY:

216630

AN XY:

726564

show subpopulations

Gnomad4 AFR exome

AF:

0.402

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.319

AC:

48553

AN:

152186

Hom.:

8043

Cov.:

AF XY:

0.318

AC XY:

23631

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.398

Gnomad4 AMR

AF:

0.322

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.277

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.292

Alfa

AF:

0.308

Hom.:

3151

Bravo

AF:

0.327

Asia WGS

AF:

0.178

AC:

622

AN:

3478

EpiCase

AF:

0.305

EpiControl

AF:

0.299

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 23, 2012	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 22, 2016	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. -

Bethlem myopathy 1A

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

Ullrich congenital muscular dystrophy 1A;CN029274:Bethlem myopathy 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

May 31, 2017

- -

Collagen 6-related myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Ullrich congenital muscular dystrophy 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.38

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over