chr21-45981846-C-G

Position:

chr21-45981846-C-G

Variant summary

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

The NM_001848.3(COL6A1):c.-5C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,574,586 control chromosomes in the GnomAD database, including 216,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18376 hom., cov: 24)

Exomes 𝑓: 0.52 ( 198437 hom. )

Consequence

COL6A1
NM_001848.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.257

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 21-45981846-C-G is Benign according to our data. Variant chr21-45981846-C-G is described in ClinVar as [Benign]. Clinvar id is 93792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45981846-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3 linkuse as main transcript	c.-5C>G		5_prime_UTR_variant	1/35	ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8 linkuse as main transcript	c.-5C>G		5_prime_UTR_variant	1/35	1	NM_001848.3	P1

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

71156

AN:

149192

Hom.:

18365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.556

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.770

Gnomad SAS

AF:

0.621

Gnomad FIN

AF:

0.562

Gnomad MID

AF:

0.660

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.539

GnomAD3 exomes

AF:

0.555

AC:

104340

AN:

188092

Hom.:

29837

AF XY:

0.557

AC XY:

57300

AN XY:

102834

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.604

Gnomad ASJ exome

AF:

0.573

Gnomad EAS exome

AF:

0.774

Gnomad SAS exome

AF:

0.604

Gnomad FIN exome

AF:

0.557

Gnomad NFE exome

AF:

0.516

Gnomad OTH exome

AF:

0.576

GnomAD4 exome

AF:

0.523

AC:

744998

AN:

1425282

Hom.:

198437

Cov.:

AF XY:

0.527

AC XY:

372074

AN XY:

706378

show subpopulations

Gnomad4 AFR exome

AF:

0.272

Gnomad4 AMR exome

AF:

0.604

Gnomad4 ASJ exome

AF:

0.580

Gnomad4 EAS exome

AF:

0.748

Gnomad4 SAS exome

AF:

0.606

Gnomad4 FIN exome

AF:

0.563

Gnomad4 NFE exome

AF:

0.509

Gnomad4 OTH exome

AF:

0.539

GnomAD4 genome

AF:

0.477

AC:

71194

AN:

149304

Hom.:

18376

Cov.:

AF XY:

0.482

AC XY:

35079

AN XY:

72772

show subpopulations

Gnomad4 AFR

AF:

0.284

Gnomad4 AMR

AF:

0.555

Gnomad4 ASJ

AF:

0.583

Gnomad4 EAS

AF:

0.770

Gnomad4 SAS

AF:

0.619

Gnomad4 FIN

AF:

0.562

Gnomad4 NFE

AF:

0.521

Gnomad4 OTH

AF:

0.544

Alfa

AF:

0.490

Hom.:

5441

Bravo

AF:

0.470

Asia WGS

AF:

0.703

AC:

2443

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 20, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2016	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. -

Collagen 6-related myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

8.7

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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