rs2277813

Positions:

• chr21-45989325-G-C
• chr21-45989325-G-A

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.858+188G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,194 control chromosomes in the GnomAD database, including 35,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (35859 hom., cov: 35)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.931

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=-0.94).
• BP6: Variant 21-45989325-G-C is Benign according to our data. Variant chr21-45989325-G-C is described in ClinVar as [Benign]. Clinvar id is 679178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3	c.858+188G>C		intron_variant		ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8	c.858+188G>C		intron_variant		1	NM_001848.3	P1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 104069 AN: 152076 Hom.: 35820 Cov.: 35

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.684 AC: 104163 AN: 152194 Hom.: 35859 Cov.: 35 AF XY: 0.683 AC XY: 50827 AN XY: 74410

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.681

Alfa AF: 0.590 Hom.: 1904

Bravo AF: 0.690

Asia WGS AF: 0.701 AC: 2438 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	-0.94
CADD	Benign	0.79
DANN	Benign	0.63

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: rs2277813; hg19: chr21-47409239;