rs59232721

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.7669-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 1,531,106 control chromosomes in the GnomAD database, including 5,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.066 ( 395 hom., cov: 32)

Exomes 𝑓: 0.086 ( 5555 hom. )

Consequence

COL6A3
NM_004369.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.827

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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-237342196-G-A is Benign according to our data. Variant chr2-237342196-G-A is described in ClinVar as [Benign]. Clinvar id is 94993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL6A3	NM_004369.4 link	c.7669-35C>T	intron_variant	Intron 36 of 43	ENST00000295550.9	NP_004360.2	P12111-1D9ZGF2Q8N4Z1Q63HQ4
COL6A3	NM_057167.4 link	c.7051-35C>T	intron_variant	Intron 35 of 42		NP_476508.2	P12111-2Q8N4Z1Q63HQ4
COL6A3	NM_057166.5 link	c.5848-35C>T	intron_variant	Intron 33 of 40		NP_476507.3	P12111-4B7ZW00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A3	ENST00000295550.9 link	c.7669-35C>T		intron_variant	Intron 36 of 43	1	NM_004369.4	ENSP00000295550.4		P12111-1

Frequencies

GnomAD3 genomes

AF:

0.0655

AC:

9965

AN:

152108

Hom.:

392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0413

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0481

Gnomad ASJ

AF:

0.0933

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0699

Gnomad FIN

AF:

0.0581

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0892

Gnomad OTH

AF:

0.0565

GnomAD3 exomes

AF:

0.0672

AC:

16305

AN:

242500

Hom.:

653

AF XY:

0.0702

AC XY:

9161

AN XY:

130578

show subpopulations

Gnomad AFR exome

AF:

0.0397

Gnomad AMR exome

AF:

0.0331

Gnomad ASJ exome

AF:

0.0980

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.0729

Gnomad FIN exome

AF:

0.0599

Gnomad NFE exome

AF:

0.0894

Gnomad OTH exome

AF:

0.0747

GnomAD4 exome

AF:

0.0860

AC:

118624

AN:

1378880

Hom.:

5555

Cov.:

AF XY:

0.0861

AC XY:

59382

AN XY:

689902

show subpopulations

Gnomad4 AFR exome

AF:

0.0381

Gnomad4 AMR exome

AF:

0.0350

Gnomad4 ASJ exome

AF:

0.0918

Gnomad4 EAS exome

AF:

0.000280

Gnomad4 SAS exome

AF:

0.0753

Gnomad4 FIN exome

AF:

0.0622

Gnomad4 NFE exome

AF:

0.0945

Gnomad4 OTH exome

AF:

0.0915

GnomAD4 genome

AF:

0.0656

AC:

9983

AN:

152226

Hom.:

395

Cov.:

AF XY:

0.0616

AC XY:

4587

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0416

Gnomad4 AMR

AF:

0.0480

Gnomad4 ASJ

AF:

0.0933

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0707

Gnomad4 FIN

AF:

0.0581

Gnomad4 NFE

AF:

0.0893

Gnomad4 OTH

AF:

0.0549

Alfa

AF:

0.0785

Hom.:

Bravo

AF:

0.0651

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

Jun 19, 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. -

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

-0.85

CADD

Benign

1.7

DANN

Benign

0.49

BranchPoint Hunter

1.0

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