rs2839077

Variant names:

Variant summary

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

The NM_001848.3(COL6A1):c.1399-32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,605,044 control chromosomes in the GnomAD database, including 222,502 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19486 hom., cov: 32)

Exomes 𝑓: 0.52 ( 203016 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.03

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 21-45997389-T-C is Benign according to our data. Variant chr21-45997389-T-C is described in ClinVar as [Benign]. Clinvar id is 93813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45997389-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3 link	c.1399-32T>C		intron_variant	Intron 20 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.1399-32T>C		intron_variant	Intron 20 of 34	1	NM_001848.3	ENSP00000355180.3		P12109
COL6A1	ENST00000683550.1 link	n.174-32T>C		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

75679

AN:

151746

Hom.:

19465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.494

Gnomad EAS

AF:

0.667

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.509

GnomAD3 exomes

AF:

0.548

AC:

137059

AN:

250246

Hom.:

39151

AF XY:

0.537

AC XY:

72848

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.384

Gnomad AMR exome

AF:

0.754

Gnomad ASJ exome

AF:

0.499

Gnomad EAS exome

AF:

0.674

Gnomad SAS exome

AF:

0.463

Gnomad FIN exome

AF:

0.511

Gnomad NFE exome

AF:

0.522

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.524

AC:

761770

AN:

1453180

Hom.:

203016

Cov.:

AF XY:

0.522

AC XY:

377565

AN XY:

723416

show subpopulations

Gnomad4 AFR exome

AF:

0.371

Gnomad4 AMR exome

AF:

0.740

Gnomad4 ASJ exome

AF:

0.496

Gnomad4 EAS exome

AF:

0.651

Gnomad4 SAS exome

AF:

0.469

Gnomad4 FIN exome

AF:

0.523

Gnomad4 NFE exome

AF:

0.522

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

AF:

0.499

AC:

75746

AN:

151864

Hom.:

19486

Cov.:

AF XY:

0.501

AC XY:

37143

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.384

Gnomad4 AMR

AF:

0.641

Gnomad4 ASJ

AF:

0.494

Gnomad4 EAS

AF:

0.668

Gnomad4 SAS

AF:

0.469

Gnomad4 FIN

AF:

0.516

Gnomad4 NFE

AF:

0.523

Gnomad4 OTH

AF:

0.513

Alfa

AF:

0.516

Hom.:

29692

Bravo

AF:

0.507

Asia WGS

AF:

0.568

AC:

1974

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 24, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 14, 2018

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Bethlem myopathy 1A

Benign:1

Jul 30, 2021

Genome-Nilou Lab

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.65

DANN

Benign

0.48

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