rs200245740

Positions:

• chr21-45999004-C-CCA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001848.3(COL6A1):​c.1674+46_1674+47dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,548,928 control chromosomes in the GnomAD database, including 71 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (34 hom., cov: 34)
  • Exomes 𝑓: 0.0030 (37 hom.)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72

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 -10 ACMG points.

• BP6: Variant 21-45999004-C-CCA is Benign according to our data. Variant chr21-45999004-C-CCA is described in ClinVar as [Benign]. Clinvar id is 258292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1954/152280) while in subpopulation AFR AF= 0.0378 (1571/41556). AF 95% confidence interval is 0.0362. There are 34 homozygotes in gnomad4. There are 957 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3	c.1674+46_1674+47dup		intron_variant		ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8	c.1674+46_1674+47dup		intron_variant		1	NM_001848.3	P1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1936 AN: 152162 Hom.: 30 Cov.: 34

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00688

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00282

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.00446 AC: 692 AN: 155114 Hom.: 7 AF XY: 0.00371 AC XY: 304 AN XY: 81898

Gnomad AFR exome AF: 0.0421

Gnomad AMR exome AF: 0.00219

Gnomad ASJ exome AF: 0.00272

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00801

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.00273

GnomAD4 exome AF: 0.00297 AC: 4147 AN: 1396648 Hom.: 37 Cov.: 32 AF XY: 0.00277 AC XY: 1907 AN XY: 688724

Gnomad4 AFR exome AF: 0.0414

Gnomad4 AMR exome AF: 0.00272

Gnomad4 ASJ exome AF: 0.00227

Gnomad4 EAS exome AF: 0.0000279

Gnomad4 SAS exome AF: 0.0000379

Gnomad4 FIN exome AF: 0.00617

Gnomad4 NFE exome AF: 0.00191

Gnomad4 OTH exome AF: 0.00521

GnomAD4 genome AF: 0.0128 AC: 1954 AN: 152280 Hom.: 34 Cov.: 34 AF XY: 0.0129 AC XY: 957 AN XY: 74470

Gnomad4 AFR AF: 0.0378

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00688

Gnomad4 NFE AF: 0.00282

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00829 Hom.: 2

Bravo AF: 0.0138

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200245740; hg19: chr21-47418918;