21-45989589-A-G

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.859-19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,611,554 control chromosomes in the GnomAD database, including 589,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57254 hom., cov: 33)

Exomes 𝑓: 0.85 ( 531914 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -3.27

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=-0.92).

BP6

Variant 21-45989589-A-G is Benign according to our data. Variant chr21-45989589-A-G is described in ClinVar as [Benign]. Clinvar id is 93891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45989589-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3 link	c.859-19A>G		intron_variant	Intron 9 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.859-19A>G		intron_variant	Intron 9 of 34	1	NM_001848.3	ENSP00000355180.3		P12109

Frequencies

GnomAD3 genomes

AF:

0.868

AC:

131902

AN:

151966

Hom.:

57210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.887

Gnomad AMI

AF:

0.865

Gnomad AMR

AF:

0.862

Gnomad ASJ

AF:

0.838

Gnomad EAS

AF:

0.926

Gnomad SAS

AF:

0.851

Gnomad FIN

AF:

0.887

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.853

Gnomad OTH

AF:

0.880

GnomAD3 exomes

AF:

0.859

AC:

214735

AN:

250032

Hom.:

92452

AF XY:

0.858

AC XY:

116356

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.886

Gnomad AMR exome

AF:

0.831

Gnomad ASJ exome

AF:

0.827

Gnomad EAS exome

AF:

0.926

Gnomad SAS exome

AF:

0.845

Gnomad FIN exome

AF:

0.880

Gnomad NFE exome

AF:

0.855

Gnomad OTH exome

AF:

0.859

GnomAD4 exome

AF:

0.853

AC:

1245414

AN:

1459472

Hom.:

531914

Cov.:

AF XY:

0.853

AC XY:

619391

AN XY:

726058

show subpopulations

Gnomad4 AFR exome

AF:

0.883

Gnomad4 AMR exome

AF:

0.836

Gnomad4 ASJ exome

AF:

0.832

Gnomad4 EAS exome

AF:

0.933

Gnomad4 SAS exome

AF:

0.846

Gnomad4 FIN exome

AF:

0.881

Gnomad4 NFE exome

AF:

0.850

Gnomad4 OTH exome

AF:

0.857

GnomAD4 genome

AF:

0.868

AC:

132005

AN:

152082

Hom.:

57254

Cov.:

AF XY:

0.868

AC XY:

64518

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.886

Gnomad4 AMR

AF:

0.862

Gnomad4 ASJ

AF:

0.838

Gnomad4 EAS

AF:

0.926

Gnomad4 SAS

AF:

0.851

Gnomad4 FIN

AF:

0.887

Gnomad4 NFE

AF:

0.853

Gnomad4 OTH

AF:

0.881

Alfa

AF:

0.853

Hom.:

80514

Bravo

AF:

0.869

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Jan 22, 2016

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 14, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Bethlem myopathy 1A

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0020

DANN

Benign

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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