Variant rs2645778 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004369.4(COL6A3):c.92-59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,582,598 control chromosomes in the GnomAD database, including 66,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11199 hom., cov: 33)

Exomes 𝑓: 0.27 ( 55352 hom. )

Consequence

COL6A3
NM_004369.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0420

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=-0.83).

BP6

Variant 2-237395263-A-G is Benign according to our data. Variant chr2-237395263-A-G is described in ClinVar as [Benign]. Clinvar id is 1248152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A3	NM_004369.4 link	c.92-59T>C		intron_variant		ENST00000295550.9	NP_004360.2	P12111-1D9ZGF2Q8N4Z1Q63HQ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A3	ENST00000295550.9 link	c.92-59T>C		intron_variant		1	NM_004369.4	ENSP00000295550.4		P12111-1

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54198

AN:

152022

Hom.:

11163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.336

GnomAD4 exome

AF:

0.271

AC:

388321

AN:

1430458

Hom.:

55352

AF XY:

0.270

AC XY:

192203

AN XY:

711620

show subpopulations

Gnomad4 AFR exome

AF:

0.584

Gnomad4 AMR exome

AF:

0.373

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.313

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.285

GnomAD4 genome

AF:

0.357

AC:

54294

AN:

152140

Hom.:

11199

Cov.:

AF XY:

0.359

AC XY:

26721

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.575

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.331

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.251

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.317

Hom.:

1780

Bravo

AF:

0.371

Asia WGS

AF:

0.344

AC:

1199

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 56% 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: 52. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.0

DANN

Benign

0.87

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