Variant 21-45986696-G-GC 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.588+19dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,544,256 control chromosomes in the GnomAD database, including 3,907 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 1493 hom., cov: 31)

Exomes 𝑓: 0.024 ( 2414 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -1.45

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 -16 ACMG points.

BP6

Variant 21-45986696-G-GC is Benign according to our data. Variant chr21-45986696-G-GC is described in ClinVar as [Benign]. Clinvar id is 93880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 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.588+19dupC		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.588+19dupC		intron_variant		1	NM_001848.3	ENSP00000355180.3		P12109

Frequencies

GnomAD3 genomes

AF:

0.0857

AC:

12998

AN:

151632

Hom.:

1492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0428

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.0993

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00709

Gnomad OTH

AF:

0.0570

GnomAD3 exomes

AF:

0.0478

AC:

7173

AN:

150210

Hom.:

509

AF XY:

0.0483

AC XY:

3848

AN XY:

79708

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.0265

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.134

Gnomad SAS exome

AF:

0.0998

Gnomad FIN exome

AF:

0.00317

Gnomad NFE exome

AF:

0.00708

Gnomad OTH exome

AF:

0.0293

GnomAD4 exome

AF:

0.0239

AC:

33290

AN:

1392506

Hom.:

2414

Cov.:

AF XY:

0.0254

AC XY:

17462

AN XY:

686934

show subpopulations

Gnomad4 AFR exome

AF:

0.266

Gnomad4 AMR exome

AF:

0.0290

Gnomad4 ASJ exome

AF:

0.0187

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.00351

Gnomad4 NFE exome

AF:

0.00585

Gnomad4 OTH exome

AF:

0.0367

GnomAD4 genome

AF:

0.0858

AC:

13015

AN:

151750

Hom.:

1493

Cov.:

AF XY:

0.0859

AC XY:

6372

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.0428

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00708

Gnomad4 OTH

AF:

0.0560

Bravo

AF:

0.0944

Asia WGS

AF:

0.100

AC:

345

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 05, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 02, 2016	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Collagen 6-related myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Bethlem myopathy 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

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