chr2-237346477-C-T

Variant names:

Variant summary

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

The NM_004369.4(COL6A3):c.7092+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,606,726 control chromosomes in the GnomAD database, including 17,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3481 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13709 hom. )

Consequence

COL6A3
NM_004369.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0190

Variant links:

Genes affected

COL6A3 (HGNC:2213): (collagen type VI alpha 3 chain) This gene encodes the alpha-3 chain, one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The alpha-3 chain of type VI collagen is much larger than the alpha-1 and -2 chains. This difference in size is largely due to an increase in the number of subdomains, similar to von Willebrand Factor type A domains, that are found in the amino terminal globular domain of all the alpha chains. These domains have been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components. Mutations in the type VI collagen genes are associated with Bethlem myopathy, a rare autosomal dominant proximal myopathy with early childhood onset. Mutations in this gene are also a cause of Ullrich congenital muscular dystrophy, also referred to as Ullrich scleroatonic muscular dystrophy, an autosomal recessive congenital myopathy that is more severe than Bethlem myopathy. Multiple transcript variants have been identified, but the full-length nature of only some of these variants has been described. [provided by RefSeq, Jun 2009]

COL6A3 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=-0.89).

BP6

Variant 2-237346477-C-T is Benign according to our data. Variant chr2-237346477-C-T is described in ClinVar as [Benign]. Clinvar id is 94979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237346477-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL6A3	NM_004369.4 link	c.7092+26G>A	intron_variant	Intron 32 of 43	ENST00000295550.9	NP_004360.2	P12111-1D9ZGF2Q8N4Z1Q63HQ4
COL6A3	NM_057167.4 link	c.6474+26G>A	intron_variant	Intron 31 of 42		NP_476508.2	P12111-2Q8N4Z1Q63HQ4
COL6A3	NM_057166.5 link	c.5271+26G>A	intron_variant	Intron 29 of 40		NP_476507.3	P12111-4B7ZW00

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A3	ENST00000295550.9 link	c.7092+26G>A	intron_variant	Intron 32 of 43	1	NM_004369.4	ENSP00000295550.4	P12111-1
COL6A3	ENST00000472056.5 link	c.5271+26G>A	intron_variant	Intron 29 of 40	1		ENSP00000418285.1	P12111-4
COL6A3	ENST00000353578.9 link	c.6474+26G>A	intron_variant	Intron 31 of 42	5		ENSP00000315873.4	P12111-2
COL6A3	ENST00000491769.1 link	n.1346+26G>A	intron_variant	Intron 9 of 19	5

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28625

AN:

151922

Hom.:

3475

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.0526

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.193

GnomAD3 exomes

AF:

0.150

AC:

37751

AN:

251186

Hom.:

3378

AF XY:

0.146

AC XY:

19823

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.0512

Gnomad SAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.130

AC:

188405

AN:

1454686

Hom.:

13709

Cov.:

AF XY:

0.129

AC XY:

93627

AN XY:

724072

show subpopulations

Gnomad4 AFR exome

AF:

0.345

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.0536

Gnomad4 SAS exome

AF:

0.145

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.141

GnomAD4 genome

AF:

0.189

AC:

28664

AN:

152040

Hom.:

3481

Cov.:

AF XY:

0.188

AC XY:

13958

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.334

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.0524

Gnomad4 SAS

AF:

0.141

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.162

Hom.:

550

Bravo

AF:

0.201

Asia WGS

AF:

0.112

AC:

392

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 33. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 05, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

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. -

Dystonia 27

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bethlem myopathy 1A

Benign:1

Jul 30, 2021

Genome-Nilou Lab

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.4

DANN

Benign

0.46

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