rs11701124

Variant summary

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

The NM_001848.3(COL6A1):c.1956+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,607,804 control chromosomes in the GnomAD database, including 193,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18779 hom., cov: 35)

Exomes 𝑓: 0.49 ( 174329 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -4.33

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=-0.83).

BP6

Variant 21-46001401-C-T is Benign according to our data. Variant chr21-46001401-C-T is described in ClinVar as [Benign]. Clinvar id is 93841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46001401-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3 linkuse as main transcript	c.1956+15C>T		intron_variant		ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8 linkuse as main transcript	c.1956+15C>T		intron_variant		1	NM_001848.3	P1

Frequencies

GnomAD3 genomes

AF:

0.494

AC:

75025

AN:

151994

Hom.:

18764

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.527

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.712

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.475

Gnomad OTH

AF:

0.500

GnomAD3 exomes

AF:

0.527

AC:

129065

AN:

245106

Hom.:

34785

AF XY:

0.524

AC XY:

69747

AN XY:

133148

show subpopulations

Gnomad AFR exome

AF:

0.472

Gnomad AMR exome

AF:

0.596

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.713

Gnomad SAS exome

AF:

0.545

Gnomad FIN exome

AF:

0.515

Gnomad NFE exome

AF:

0.477

Gnomad OTH exome

AF:

0.532

GnomAD4 exome

AF:

0.486

AC:

707927

AN:

1455692

Hom.:

174329

Cov.:

AF XY:

0.488

AC XY:

353704

AN XY:

724350

show subpopulations

Gnomad4 AFR exome

AF:

0.467

Gnomad4 AMR exome

AF:

0.592

Gnomad4 ASJ exome

AF:

0.545

Gnomad4 EAS exome

AF:

0.691

Gnomad4 SAS exome

AF:

0.544

Gnomad4 FIN exome

AF:

0.515

Gnomad4 NFE exome

AF:

0.467

Gnomad4 OTH exome

AF:

0.505

GnomAD4 genome

AF:

0.494

AC:

75087

AN:

152112

Hom.:

18779

Cov.:

AF XY:

0.496

AC XY:

36869

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.469

Gnomad4 AMR

AF:

0.527

Gnomad4 ASJ

AF:

0.541

Gnomad4 EAS

AF:

0.712

Gnomad4 SAS

AF:

0.554

Gnomad4 FIN

AF:

0.505

Gnomad4 NFE

AF:

0.475

Gnomad4 OTH

AF:

0.503

Alfa

AF:

0.497

Hom.:

3485

Bravo

AF:

0.494

Asia WGS

AF:

0.625

AC:

2173

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 14, 2014	- -
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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Bethlem myopathy 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Collagen 6-related myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

0.41

Dann

Benign

0.84

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