Variant 21-46002730-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001848.3(COL6A1):c.2434+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,532,036 control chromosomes in the GnomAD database, including 96,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8640 hom., cov: 36)

Exomes 𝑓: 0.34 ( 87876 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.735

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 21-46002730-G-A is Benign according to our data. Variant chr21-46002730-G-A is described in ClinVar as [Benign]. Clinvar id is 93855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46002730-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3 link	c.2434+20G>A		intron_variant	Intron 33 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.2434+20G>A		intron_variant	Intron 33 of 34	1	NM_001848.3	ENSP00000355180.3		P12109

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48698

AN:

151066

Hom.:

8630

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.386

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.342

GnomAD3 exomes

AF:

0.383

AC:

87646

AN:

229102

Hom.:

19650

AF XY:

0.378

AC XY:

47323

AN XY:

125202

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.385

Gnomad EAS exome

AF:

0.642

Gnomad SAS exome

AF:

0.382

Gnomad FIN exome

AF:

0.376

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.383

GnomAD4 exome

AF:

0.343

AC:

473683

AN:

1380850

Hom.:

87876

Cov.:

AF XY:

0.346

AC XY:

237633

AN XY:

687702

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.526

Gnomad4 ASJ exome

AF:

0.386

Gnomad4 EAS exome

AF:

0.626

Gnomad4 SAS exome

AF:

0.396

Gnomad4 FIN exome

AF:

0.396

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.358

GnomAD4 genome

AF:

0.322

AC:

48721

AN:

151186

Hom.:

8640

Cov.:

AF XY:

0.327

AC XY:

24175

AN XY:

73866

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.386

Gnomad4 EAS

AF:

0.633

Gnomad4 SAS

AF:

0.398

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.346

Alfa

AF:

0.330

Hom.:

1377

Bravo

AF:

0.322

Asia WGS

AF:

0.485

AC:

1659

AN:

3424

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 09, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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. -

Bethlem myopathy 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 03, 2025

- -

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

-0.86

CADD

Benign

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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