chr21-45991017-T-C

Position:

chr21-45991017-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000361866.8(COL6A1):c.1095T>C(p.Gly365=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,612,982 control chromosomes in the GnomAD database, including 248,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27784 hom., cov: 33)

Exomes 𝑓: 0.55 ( 220481 hom. )

Consequence

COL6A1
ENST00000361866.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -1.89

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 21-45991017-T-C is Benign according to our data. Variant chr21-45991017-T-C is described in ClinVar as [Benign]. Clinvar id is 93805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45991017-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 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.1095T>C	p.Gly365=	synonymous_variant	15/35	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.1095T>C	p.Gly365=	synonymous_variant	15/35	1	NM_001848.3	ENSP00000355180	P1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90329

AN:

151928

Hom.:

27743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.752

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.519

Gnomad ASJ

AF:

0.585

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.512

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.572

GnomAD3 exomes

AF:

0.523

AC:

130962

AN:

250540

Hom.:

35341

AF XY:

0.522

AC XY:

70911

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.756

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.571

Gnomad EAS exome

AF:

0.348

Gnomad SAS exome

AF:

0.517

Gnomad FIN exome

AF:

0.492

Gnomad NFE exome

AF:

0.550

Gnomad OTH exome

AF:

0.518

GnomAD4 exome

AF:

0.546

AC:

798217

AN:

1460936

Hom.:

220481

Cov.:

AF XY:

0.546

AC XY:

396517

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.758

Gnomad4 AMR exome

AF:

0.435

Gnomad4 ASJ exome

AF:

0.574

Gnomad4 EAS exome

AF:

0.353

Gnomad4 SAS exome

AF:

0.519

Gnomad4 FIN exome

AF:

0.490

Gnomad4 NFE exome

AF:

0.556

Gnomad4 OTH exome

AF:

0.548

GnomAD4 genome

AF:

0.595

AC:

90438

AN:

152046

Hom.:

27784

Cov.:

AF XY:

0.589

AC XY:

43760

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.752

Gnomad4 AMR

AF:

0.519

Gnomad4 ASJ

AF:

0.585

Gnomad4 EAS

AF:

0.345

Gnomad4 SAS

AF:

0.511

Gnomad4 FIN

AF:

0.495

Gnomad4 NFE

AF:

0.558

Gnomad4 OTH

AF:

0.572

Alfa

AF:

0.566

Hom.:

17264

Bravo

AF:

0.603

Asia WGS

AF:

0.449

AC:

1560

AN:

3478

EpiCase

AF:

0.551

EpiControl

AF:

0.551

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

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, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Ullrich congenital muscular dystrophy 1A;CN029274:Bethlem myopathy 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

May 31, 2017

- -

Collagen 6-related myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

-0.85

CADD

Benign

0.13

DANN

Benign

0.35

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