Variant 21-45997518-A-AG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001848.3(COL6A1):c.1461+41dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,574,486 control chromosomes in the GnomAD database, including 433,533 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41194 hom., cov: 0)

Exomes 𝑓: 0.74 ( 392339 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.134

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:

COL6A1 (HGNC:):

COL6A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 21-45997518-A-AG is Benign according to our data. Variant chr21-45997518-A-AG is described in ClinVar as [Benign]. Clinvar id is 93816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.776 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.1461+41dupG		intron_variant		ENST00000361866.8	NP_001839.2	P12109A0A384P5H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8 linkuse as main transcript	c.1461+41dupG		intron_variant		1	NM_001848.3	ENSP00000355180.3		P12109
COL6A1	ENST00000683550.1 linkuse as main transcript	n.236+41dupG		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.737

AC:

111356

AN:

151074

Hom.:

41155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.763

Gnomad AMR

AF:

0.787

Gnomad ASJ

AF:

0.742

Gnomad EAS

AF:

0.745

Gnomad SAS

AF:

0.684

Gnomad FIN

AF:

0.811

Gnomad MID

AF:

0.660

Gnomad NFE

AF:

0.745

Gnomad OTH

AF:

0.727

GnomAD3 exomes

AF:

0.754

AC:

183575

AN:

243492

Hom.:

69773

AF XY:

0.746

AC XY:

99170

AN XY:

132854

show subpopulations

Gnomad AFR exome

AF:

0.695

Gnomad AMR exome

AF:

0.868

Gnomad ASJ exome

AF:

0.752

Gnomad EAS exome

AF:

0.730

Gnomad SAS exome

AF:

0.665

Gnomad FIN exome

AF:

0.811

Gnomad NFE exome

AF:

0.744

Gnomad OTH exome

AF:

0.757

GnomAD4 exome

AF:

0.744

AC:

1059363

AN:

1423294

Hom.:

392339

Cov.:

AF XY:

0.742

AC XY:

526677

AN XY:

709912

show subpopulations

Gnomad4 AFR exome

AF:

0.695

Gnomad4 AMR exome

AF:

0.861

Gnomad4 ASJ exome

AF:

0.751

Gnomad4 EAS exome

AF:

0.730

Gnomad4 SAS exome

AF:

0.668

Gnomad4 FIN exome

AF:

0.820

Gnomad4 NFE exome

AF:

0.744

Gnomad4 OTH exome

AF:

0.746

GnomAD4 genome

AF:

0.737

AC:

111446

AN:

151192

Hom.:

41194

Cov.:

AF XY:

0.739

AC XY:

54547

AN XY:

73846

show subpopulations

Gnomad4 AFR

AF:

0.692

Gnomad4 AMR

AF:

0.788

Gnomad4 ASJ

AF:

0.742

Gnomad4 EAS

AF:

0.745

Gnomad4 SAS

AF:

0.684

Gnomad4 FIN

AF:

0.811

Gnomad4 NFE

AF:

0.745

Gnomad4 OTH

AF:

0.726

Alfa

AF:

0.717

Hom.:

4007

Asia WGS

AF:

0.709

AC:

2465

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 24, 2012	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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