Variant 21-45994015-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001848.3(COL6A1):c.1336-152G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 804,036 control chromosomes in the GnomAD database, including 240,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.78 ( 46409 hom., cov: 33)

Exomes 𝑓: 0.77 ( 194111 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20

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:

COL6A1 (HGNC:):

COL6A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 21-45994015-G-T is Benign according to our data. Variant chr21-45994015-G-T is described in ClinVar as [Benign]. Clinvar id is 679939.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A1	NM_001848.3 linkuse as main transcript	c.1336-152G>T		intron_variant		ENST00000361866.8	NP_001839.2	P12109A0A384P5H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8 linkuse as main transcript	c.1336-152G>T		intron_variant		1	NM_001848.3	ENSP00000355180.3		P12109
COL6A1	ENST00000683550.1 linkuse as main transcript	n.-42G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.779

AC:

118486

AN:

152046

Hom.:

46365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.808

Gnomad AMI

AF:

0.765

Gnomad AMR

AF:

0.819

Gnomad ASJ

AF:

0.738

Gnomad EAS

AF:

0.871

Gnomad SAS

AF:

0.763

Gnomad FIN

AF:

0.804

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.747

Gnomad OTH

AF:

0.750

GnomAD4 exome

AF:

0.770

AC:

501861

AN:

651872

Hom.:

194111

AF XY:

0.768

AC XY:

263080

AN XY:

342512

show subpopulations

Gnomad4 AFR exome

AF:

0.810

Gnomad4 AMR exome

AF:

0.871

Gnomad4 ASJ exome

AF:

0.752

Gnomad4 EAS exome

AF:

0.880

Gnomad4 SAS exome

AF:

0.761

Gnomad4 FIN exome

AF:

0.811

Gnomad4 NFE exome

AF:

0.749

Gnomad4 OTH exome

AF:

0.766

GnomAD4 genome

AF:

0.779

AC:

118578

AN:

152164

Hom.:

46409

Cov.:

AF XY:

0.782

AC XY:

58137

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.807

Gnomad4 AMR

AF:

0.819

Gnomad4 ASJ

AF:

0.738

Gnomad4 EAS

AF:

0.871

Gnomad4 SAS

AF:

0.764

Gnomad4 FIN

AF:

0.804

Gnomad4 NFE

AF:

0.747

Gnomad4 OTH

AF:

0.751

Alfa

AF:

0.752

Hom.:

39016

Bravo

AF:

0.783

Asia WGS

AF:

0.801

AC:

2785

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.87

CADD

Benign

0.16

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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