Variant rs148766287 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001848.3(COL6A1):c.428+39C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,588,504 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 13 hom., cov: 35)

Exomes 𝑓: 0.013 ( 180 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.211

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 21-45984508-C-G is Benign according to our data. Variant chr21-45984508-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 93874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45984508-C-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00942 (1436/152370) while in subpopulation NFE AF= 0.0146 (995/68038). AF 95% confidence interval is 0.0139. There are 13 homozygotes in gnomad4. There are 709 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3 linkuse as main transcript	c.428+39C>G		intron_variant		ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8 linkuse as main transcript	c.428+39C>G		intron_variant		1	NM_001848.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00945

AC:

1439

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.0105

AC:

2439

AN:

233246

Hom.:

AF XY:

0.0105

AC XY:

1345

AN XY:

128176

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00274

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00271

Gnomad FIN exome

AF:

0.0215

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0132

AC:

18981

AN:

1436134

Hom.:

180

Cov.:

AF XY:

0.0129

AC XY:

9204

AN XY:

715584

show subpopulations

Gnomad4 AFR exome

AF:

0.00214

Gnomad4 AMR exome

AF:

0.00271

Gnomad4 ASJ exome

AF:

0.00288

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00365

Gnomad4 FIN exome

AF:

0.0209

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.00942

AC:

1436

AN:

152370

Hom.:

Cov.:

AF XY:

0.00952

AC XY:

709

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00269

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0189

Gnomad4 NFE

AF:

0.0146

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00539

Hom.:

Bravo

AF:

0.00807

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 05, 2012	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

DANN

Benign

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over