21-45997664-A-G

Variant names:

Variant summary

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

The NM_001848.3(COL6A1):c.1462-36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,569,028 control chromosomes in the GnomAD database, including 77,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.34 ( 9489 hom., cov: 34)

Exomes 𝑓: 0.31 ( 68458 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.31

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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 21-45997664-A-G is Benign according to our data. Variant chr21-45997664-A-G is described in ClinVar as [Benign]. Clinvar id is 93817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45997664-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3 link	c.1462-36A>G		intron_variant	Intron 21 of 34	ENST00000361866.8	NP_001839.2	P12109A0A384P5H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8 link	c.1462-36A>G		intron_variant	Intron 21 of 34	1	NM_001848.3	ENSP00000355180.3		P12109
COL6A1	ENST00000683550.1 link	n.237-36A>G		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51891

AN:

151834

Hom.:

9476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.465

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.318

GnomAD3 exomes

AF:

0.288

AC:

52130

AN:

181320

Hom.:

7928

AF XY:

0.281

AC XY:

27279

AN XY:

97184

show subpopulations

Gnomad AFR exome

AF:

0.462

Gnomad AMR exome

AF:

0.304

Gnomad ASJ exome

AF:

0.234

Gnomad EAS exome

AF:

0.151

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.280

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.277

GnomAD4 exome

AF:

0.307

AC:

435528

AN:

1417076

Hom.:

68458

Cov.:

AF XY:

0.304

AC XY:

212915

AN XY:

701030

show subpopulations

Gnomad4 AFR exome

AF:

0.473

Gnomad4 AMR exome

AF:

0.302

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.316

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.342

AC:

51947

AN:

151952

Hom.:

9489

Cov.:

AF XY:

0.340

AC XY:

25280

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.465

Gnomad4 AMR

AF:

0.332

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.166

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.285

Gnomad4 NFE

AF:

0.309

Gnomad4 OTH

AF:

0.314

Alfa

AF:

0.307

Hom.:

1348

Bravo

AF:

0.352

Asia WGS

AF:

0.187

AC:

653

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Aug 24, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Bethlem myopathy 1A

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ullrich congenital muscular dystrophy 1A

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.76

DANN

Benign

0.26

BranchPoint Hunter

1.0

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