rs2850173

Variant names:

• chr21-45992837-A-C
• rs2850173
• NM_001848.3:c.1335+27A>C

Your query was ambiguous. Multiple possible variants found:

• chr21-45992837-A-C
• chr21-45992837-A-G
• chr21-45992837-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001848.3(COL6A1):​c.1335+27A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 1,571,902 control chromosomes in the GnomAD database, including 583,855 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (58848 hom., cov: 34)
  • Exomes 𝑓: 0.86 (525007 hom.)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.34
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• collagen 6-related myopathy

  Inheritance: AD, AR Classification: DEFINITIVE Submitted by: ClinGen
• Bethlem myopathy 1A

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P
• Ullrich congenital muscular dystrophy 1A

  Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• Bethlem myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Ullrich congenital muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-45992837-A-C is Benign according to our data. Variant chr21-45992837-A-C is described in ClinVar as Benign. ClinVar VariationId is 93811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3	c.1335+27A>C		intron_variant	Intron 19 of 34	ENST00000361866.8	NP_001839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8	c.1335+27A>C		intron_variant	Intron 19 of 34	1	NM_001848.3	ENSP00000355180.3

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133594 AN: 152100 Hom.: 58785 Cov.: 34

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.849

GnomAD2 exomes AF: 0.861 AC: 161350 AN: 187312 AF XY: 0.854

Gnomad AFR exome AF: 0.921

Gnomad AMR exome AF: 0.925

Gnomad ASJ exome AF: 0.814

Gnomad EAS exome AF: 0.857

Gnomad FIN exome AF: 0.886

Gnomad NFE exome AF: 0.855

Gnomad OTH exome AF: 0.861

GnomAD4 exome AF: 0.859 AC: 1220047 AN: 1419684 Hom.: 525007 Cov.: 34 AF XY: 0.856 AC XY: 601530 AN XY: 702378

African (AFR) AF: 0.926 AC: 30457 AN: 32906

American (AMR) AF: 0.921 AC: 35666 AN: 38720

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 20333 AN: 25312

East Asian (EAS) AF: 0.877 AC: 33526 AN: 38212

South Asian (SAS) AF: 0.786 AC: 63659 AN: 80992

European-Finnish (FIN) AF: 0.889 AC: 44022 AN: 49544

Middle Eastern (MID) AF: 0.789 AC: 4367 AN: 5538

European-Non Finnish (NFE) AF: 0.861 AC: 937905 AN: 1089652

Other (OTH) AF: 0.852 AC: 50112 AN: 58808

GnomAD4 genome AF: 0.878 AC: 133714 AN: 152218 Hom.: 58848 Cov.: 34 AF XY: 0.878 AC XY: 65318 AN XY: 74424

African (AFR) AF: 0.922 AC: 38321 AN: 41552

American (AMR) AF: 0.905 AC: 13838 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2747 AN: 3472

East Asian (EAS) AF: 0.871 AC: 4474 AN: 5136

South Asian (SAS) AF: 0.785 AC: 3792 AN: 4830

European-Finnish (FIN) AF: 0.886 AC: 9415 AN: 10630

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58364 AN: 67988

Other (OTH) AF: 0.848 AC: 1792 AN: 2112

Alfa AF: 0.864 Hom.: 10423

Bravo AF: 0.883

Asia WGS AF: 0.825 AC: 2872 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Aug 27, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Bethlem myopathy 1A Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ullrich congenital muscular dystrophy 1A Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2850173; hg19: chr21-47412751;