rs741956

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001848.3(COL6A1):c.429-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,551,888 control chromosomes in the GnomAD database, including 42,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3057 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39057 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.48

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 21-45986507-G-A is Benign according to our data. Variant chr21-45986507-G-A is described in ClinVar as [Benign]. Clinvar id is 93876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45986507-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3 link	c.429-19G>A		intron_variant	Intron 3 of 34	ENST00000361866.8	NP_001839.2	P12109A0A384P5H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8 link	c.429-19G>A		intron_variant	Intron 3 of 34	1	NM_001848.3	ENSP00000355180.3		P12109

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28093

AN:

151974

Hom.:

3055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.206

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.00830

Gnomad SAS

AF:

0.0966

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.182

AC:

29123

AN:

159964

Hom.:

3247

AF XY:

0.180

AC XY:

15238

AN XY:

84488

show subpopulations

Gnomad AFR exome

AF:

0.0976

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.00567

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.228

AC:

319313

AN:

1399796

Hom.:

39057

Cov.:

AF XY:

0.224

AC XY:

154871

AN XY:

690758

show subpopulations

Gnomad4 AFR exome

AF:

0.0981

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.00618

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.185

AC:

28105

AN:

152092

Hom.:

3057

Cov.:

AF XY:

0.184

AC XY:

13691

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.00871

Gnomad4 SAS

AF:

0.0975

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.133

Hom.:

373

Bravo

AF:

0.176

Asia WGS

AF:

0.0540

AC:

190

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 05, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 09, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Bethlem myopathy 1A

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ullrich congenital muscular dystrophy 1A

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.054

DANN

Benign

0.59

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