rs202231424

chr21-45989048-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001848.3(COL6A1):c.805-36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00998 in 1,604,462 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0080 (7 hom., cov: 33)
  • Exomes 𝑓: 0.010 (106 hom.)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.41

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 21-45989048-G-A is Benign according to our data. Variant chr21-45989048-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00798 (1216/152302) while in subpopulation AMR AF= 0.0143 (219/15304). AF 95% confidence interval is 0.0128. There are 7 homozygotes in gnomad4. There are 561 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3	c.805-36G>A		intron_variant		ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8	c.805-36G>A		intron_variant		1	NM_001848.3	P1

Frequencies

GnomAD3 genomes AF: 0.00799 AC: 1216 AN: 152184 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00263

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00805 AC: 1964 AN: 244070 Hom.: 13 AF XY: 0.00763 AC XY: 1012 AN XY: 132648

Gnomad AFR exome AF: 0.00279

Gnomad AMR exome AF: 0.0111

Gnomad ASJ exome AF: 0.00507

Gnomad EAS exome AF: 0.000277

Gnomad SAS exome AF: 0.00125

Gnomad FIN exome AF: 0.00353

Gnomad NFE exome AF: 0.0121

Gnomad OTH exome AF: 0.00876

GnomAD4 exome AF: 0.0102 AC: 14799 AN: 1452160 Hom.: 106 Cov.: 30 AF XY: 0.00980 AC XY: 7072 AN XY: 721814

Gnomad4 AFR exome AF: 0.00215

Gnomad4 AMR exome AF: 0.0113

Gnomad4 ASJ exome AF: 0.00550

Gnomad4 EAS exome AF: 0.000203

Gnomad4 SAS exome AF: 0.00105

Gnomad4 FIN exome AF: 0.00472

Gnomad4 NFE exome AF: 0.0120

Gnomad4 OTH exome AF: 0.00795

GnomAD4 genome AF: 0.00798 AC: 1216 AN: 152302 Hom.: 7 Cov.: 33 AF XY: 0.00753 AC XY: 561 AN XY: 74472

Gnomad4 AFR AF: 0.00262

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00873 Hom.: 2

Bravo AF: 0.00836

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.16
Dann	Benign	0.59

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: rs202231424; hg19: chr21-47408962;