Variant chr21-45991080-C-T 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.1119+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00903 in 1,606,404 control chromosomes in the GnomAD database, including 899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 76 hom., cov: 33)

Exomes 𝑓: 0.0091 ( 823 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.33

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=-0.86).

BP6

Variant 21-45991080-C-T is Benign according to our data. Variant chr21-45991080-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45991080-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 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.1119+39C>T		intron_variant		ENST00000361866.8	NP_001839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8 linkuse as main transcript	c.1119+39C>T		intron_variant		1	NM_001848.3	ENSP00000355180	P1

Frequencies

GnomAD3 genomes

AF:

0.00852

AC:

1297

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.0429

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.0183

AC:

4525

AN:

247546

Hom.:

202

AF XY:

0.0185

AC XY:

2484

AN XY:

134608

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.00542

Gnomad EAS exome

AF:

0.139

Gnomad SAS exome

AF:

0.0422

Gnomad FIN exome

AF:

0.00269

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.0117

GnomAD4 exome

AF:

0.00909

AC:

13215

AN:

1454102

Hom.:

823

Cov.:

AF XY:

0.00991

AC XY:

7174

AN XY:

723736

show subpopulations

Gnomad4 AFR exome

AF:

0.000511

Gnomad4 AMR exome

AF:

0.0116

Gnomad4 ASJ exome

AF:

0.00606

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.0423

Gnomad4 FIN exome

AF:

0.00279

Gnomad4 NFE exome

AF:

0.000702

Gnomad4 OTH exome

AF:

0.0114

GnomAD4 genome

AF:

0.00850

AC:

1295

AN:

152302

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

770

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.0427

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00398

Hom.:

Bravo

AF:

0.00905

Asia WGS

AF:

0.0690

AC:

238

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Likely 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

-0.86

CADD

Benign

1.9

DANN

Benign

0.68

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