rs12052971

Positions:

• chr2-237390587-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004369.4(COL6A3):​c.710-2403C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,116 control chromosomes in the GnomAD database, including 10,740 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (10740 hom., cov: 32)
• Consequence: COL6A3 NM_004369.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A3	NM_004369.4	c.710-2403C>T		intron_variant		ENST00000295550.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A3	ENST00000295550.9	c.710-2403C>T		intron_variant		1	NM_004369.4	P1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53381 AN: 151998 Hom.: 10702 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.352 AC: 53482 AN: 152116 Hom.: 10740 Cov.: 32 AF XY: 0.354 AC XY: 26356 AN XY: 74362

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.334

Alfa AF: 0.335 Hom.: 1790

Bravo AF: 0.365

Asia WGS AF: 0.339 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.66
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs12052971; hg19: chr2-238299230;