chr21-45997781-G-C

Position:

chr21-45997781-G-C

Variant summary

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

The NM_001848.3(COL6A1):c.1524+19G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 1,569,514 control chromosomes in the GnomAD database, including 6,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 639 hom., cov: 35)

Exomes 𝑓: 0.087 ( 5937 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.15

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=-0.91).

BP6

Variant 21-45997781-G-C is Benign according to our data. Variant chr21-45997781-G-C is described in ClinVar as [Benign]. Clinvar id is 93821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45997781-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3 linkuse as main transcript	c.1524+19G>C		intron_variant		ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8 linkuse as main transcript	c.1524+19G>C		intron_variant		1	NM_001848.3	P1
COL6A1	ENST00000683550.1 linkuse as main transcript	n.299+19G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0865

AC:

13161

AN:

152090

Hom.:

635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0588

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.0729

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.0743

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0825

Gnomad OTH

AF:

0.0970

GnomAD3 exomes

AF:

0.101

AC:

17918

AN:

177312

Hom.:

1040

AF XY:

0.0970

AC XY:

9217

AN XY:

95050

show subpopulations

Gnomad AFR exome

AF:

0.0604

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.0656

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.0716

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.0840

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.0869

AC:

123101

AN:

1417306

Hom.:

5937

Cov.:

AF XY:

0.0863

AC XY:

60507

AN XY:

701214

show subpopulations

Gnomad4 AFR exome

AF:

0.0554

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.0647

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.0704

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.0824

Gnomad4 OTH exome

AF:

0.0895

GnomAD4 genome

AF:

0.0866

AC:

13177

AN:

152208

Hom.:

639

Cov.:

AF XY:

0.0876

AC XY:

6519

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0587

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.0729

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.0745

Gnomad4 FIN

AF:

0.107

Gnomad4 NFE

AF:

0.0826

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0432

Hom.:

Bravo

AF:

0.0883

Asia WGS

AF:

0.155

AC:

539

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 31, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Bethlem myopathy 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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

-0.91

CADD

Benign

0.010

DANN

Benign

0.34

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