Variant 21-46000812-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001848.3(COL6A1):c.1822+45C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,610,990 control chromosomes in the GnomAD database, including 589,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54298 hom., cov: 36)

Exomes 𝑓: 0.86 ( 535408 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.133

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 21-46000812-C-G is Benign according to our data. Variant chr21-46000812-C-G is described in ClinVar as [Benign]. Clinvar id is 93832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46000812-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.877 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.1822+45C>G		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.1822+45C>G		intron_variant		1	NM_001848.3	ENSP00000355180.3		P12109
COL6A1	ENST00000466285.1 linkuse as main transcript	n.384C>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.844

AC:

128366

AN:

152148

Hom.:

54253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.802

Gnomad AMI

AF:

0.827

Gnomad AMR

AF:

0.889

Gnomad ASJ

AF:

0.798

Gnomad EAS

AF:

0.873

Gnomad SAS

AF:

0.785

Gnomad FIN

AF:

0.886

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.858

Gnomad OTH

AF:

0.820

GnomAD3 exomes

AF:

0.854

AC:

214197

AN:

250872

Hom.:

91671

AF XY:

0.849

AC XY:

115209

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.800

Gnomad AMR exome

AF:

0.919

Gnomad ASJ exome

AF:

0.809

Gnomad EAS exome

AF:

0.859

Gnomad SAS exome

AF:

0.785

Gnomad FIN exome

AF:

0.885

Gnomad NFE exome

AF:

0.858

Gnomad OTH exome

AF:

0.853

GnomAD4 exome

AF:

0.856

AC:

1248815

AN:

1458724

Hom.:

535408

Cov.:

AF XY:

0.853

AC XY:

619474

AN XY:

725838

show subpopulations

Gnomad4 AFR exome

AF:

0.800

Gnomad4 AMR exome

AF:

0.914

Gnomad4 ASJ exome

AF:

0.804

Gnomad4 EAS exome

AF:

0.880

Gnomad4 SAS exome

AF:

0.788

Gnomad4 FIN exome

AF:

0.890

Gnomad4 NFE exome

AF:

0.861

Gnomad4 OTH exome

AF:

0.842

GnomAD4 genome

AF:

0.844

AC:

128464

AN:

152266

Hom.:

54298

Cov.:

AF XY:

0.846

AC XY:

62964

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.802

Gnomad4 AMR

AF:

0.890

Gnomad4 ASJ

AF:

0.798

Gnomad4 EAS

AF:

0.873

Gnomad4 SAS

AF:

0.786

Gnomad4 FIN

AF:

0.886

Gnomad4 NFE

AF:

0.858

Gnomad4 OTH

AF:

0.820

Alfa

AF:

0.844

Hom.:

5776

Bravo

AF:

0.875

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 24, 2012	- -

not provided

Benign:2

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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.4

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