Variant chr21-45992926-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.1335+116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 928,246 control chromosomes in the GnomAD database, including 58,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8350 hom., cov: 34)

Exomes 𝑓: 0.35 ( 50124 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.433

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=-0.97).

BP6

Variant 21-45992926-C-T is Benign according to our data. Variant chr21-45992926-C-T is described in ClinVar as [Benign]. Clinvar id is 679937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 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.1335+116C>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.1335+116C>T		intron_variant		1	NM_001848.3	ENSP00000355180.3		P12109

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46826

AN:

151974

Hom.:

8344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.386

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.333

GnomAD4 exome

AF:

0.351

AC:

272400

AN:

776154

Hom.:

50124

AF XY:

0.353

AC XY:

139819

AN XY:

396366

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.496

Gnomad4 ASJ exome

AF:

0.368

Gnomad4 EAS exome

AF:

0.615

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.391

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.351

GnomAD4 genome

AF:

0.308

AC:

46837

AN:

152092

Hom.:

8350

Cov.:

AF XY:

0.314

AC XY:

23305

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.418

Gnomad4 ASJ

AF:

0.370

Gnomad4 EAS

AF:

0.633

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.386

Gnomad4 NFE

AF:

0.330

Gnomad4 OTH

AF:

0.337

Alfa

AF:

0.315

Hom.:

1603

Bravo

AF:

0.305

Asia WGS

AF:

0.503

AC:

1746

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

-0.97

CADD

Benign

2.1

DANN

Benign

0.55

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