rs2075893

chr21-45992926-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001848.3(COL6A1):c.1335+116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 928,246 control chromosomes in the GnomAD database, including 58,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (8350 hom., cov: 34)
  • Exomes 𝑓: 0.35 (50124 hom.)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.433

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 21-45992926-C-T is Benign according to our data. Variant chr21-45992926-C-T is described in ClinVar as [Benign]. Clinvar id is 679937.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3	c.1335+116C>T		intron_variant		ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8	c.1335+116C>T		intron_variant		1	NM_001848.3	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46826 AN: 151974 Hom.: 8344 Cov.: 34

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.351 AC: 272400 AN: 776154 Hom.: 50124 AF XY: 0.353 AC XY: 139819 AN XY: 396366

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.496

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.615

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.308 AC: 46837 AN: 152092 Hom.: 8350 Cov.: 34 AF XY: 0.314 AC XY: 23305 AN XY: 74336

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.337

Alfa AF: 0.315 Hom.: 1603

Bravo AF: 0.305

Asia WGS AF: 0.503 AC: 1746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.1
Dann	Benign	0.55

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: rs2075893; hg19: chr21-47412840; COSMIC: COSV62611344;