rs3746993

Positions:

Variant summary

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

The NM_001848.3(COL6A1):c.428+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 1,605,828 control chromosomes in the GnomAD database, including 589,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57704 hom., cov: 35)

Exomes 𝑓: 0.85 ( 531315 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -3.77

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 21-45984483-A-G is Benign according to our data. Variant chr21-45984483-A-G is described in ClinVar as [Benign]. Clinvar id is 93873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45984483-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 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.428+14A>G		intron_variant		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.428+14A>G		intron_variant		1	NM_001848.3	ENSP00000355180	P1

Frequencies

GnomAD3 genomes

AF:

0.870

AC:

132463

AN:

152190

Hom.:

57653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.893

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.862

Gnomad ASJ

AF:

0.839

Gnomad EAS

AF:

0.925

Gnomad SAS

AF:

0.860

Gnomad FIN

AF:

0.887

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.854

Gnomad OTH

AF:

0.881

GnomAD3 exomes

AF:

0.860

AC:

207620

AN:

241302

Hom.:

89526

AF XY:

0.859

AC XY:

113376

AN XY:

131914

show subpopulations

Gnomad AFR exome

AF:

0.895

Gnomad AMR exome

AF:

0.829

Gnomad ASJ exome

AF:

0.827

Gnomad EAS exome

AF:

0.923

Gnomad SAS exome

AF:

0.854

Gnomad FIN exome

AF:

0.883

Gnomad NFE exome

AF:

0.856

Gnomad OTH exome

AF:

0.860

GnomAD4 exome

AF:

0.855

AC:

1242131

AN:

1453520

Hom.:

531315

Cov.:

AF XY:

0.855

AC XY:

618179

AN XY:

723386

show subpopulations

Gnomad4 AFR exome

AF:

0.891

Gnomad4 AMR exome

AF:

0.835

Gnomad4 ASJ exome

AF:

0.832

Gnomad4 EAS exome

AF:

0.941

Gnomad4 SAS exome

AF:

0.855

Gnomad4 FIN exome

AF:

0.884

Gnomad4 NFE exome

AF:

0.850

Gnomad4 OTH exome

AF:

0.857

GnomAD4 genome

AF:

0.870

AC:

132573

AN:

152308

Hom.:

57704

Cov.:

AF XY:

0.870

AC XY:

64771

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.893

Gnomad4 AMR

AF:

0.862

Gnomad4 ASJ

AF:

0.839

Gnomad4 EAS

AF:

0.926

Gnomad4 SAS

AF:

0.860

Gnomad4 FIN

AF:

0.887

Gnomad4 NFE

AF:

0.854

Gnomad4 OTH

AF:

0.882

Alfa

AF:

0.859

Hom.:

10329

Bravo

AF:

0.870

Asia WGS

AF:

0.903

AC:

3140

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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	-	- -
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, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 14, 2014	- -
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	- -

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. -

Ullrich congenital muscular dystrophy 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.11

DANN

Benign

0.46

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