rs2236487

Positions:

• chr21-46002765-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001848.3(COL6A1):​c.2434+55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,487,522 control chromosomes in the GnomAD database, including 96,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8288 hom., cov: 35)
  • Exomes 𝑓: 0.35 (87717 hom.)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.454

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]

COL6A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 21-46002765-G-A is Benign according to our data. Variant chr21-46002765-G-A is described in ClinVar as [Benign]. Clinvar id is 93856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46002765-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A1	NM_001848.3	c.2434+55G>A		intron_variant		ENST00000361866.8	NP_001839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8	c.2434+55G>A		intron_variant		1	NM_001848.3	ENSP00000355180.3

Frequencies

GnomAD3 genomes AF: 0.309 AC: 45862 AN: 148494 Hom.: 8281 Cov.: 35

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.345 AC: 462219 AN: 1338912 Hom.: 87717 AF XY: 0.348 AC XY: 232732 AN XY: 668238

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.521

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.392

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.309 AC: 45879 AN: 148610 Hom.: 8288 Cov.: 35 AF XY: 0.314 AC XY: 22838 AN XY: 72678

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.346

Alfa AF: 0.302 Hom.: 739

Bravo AF: 0.302

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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 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. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 23, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.73

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: rs2236487; hg19: chr21-47422679;