chr21-45986507-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001848.3(COL6A1):c.429-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,551,888 control chromosomes in the GnomAD database, including 42,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3057 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39057 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.48

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

collagen 6-related myopathy
Inheritance: AD, AR Classification: DEFINITIVE Submitted by: ClinGen
Bethlem myopathy 1A
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P
Ullrich congenital muscular dystrophy 1A
Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
Bethlem myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Ullrich congenital muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

COL6A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 21-45986507-G-A is Benign according to our data. Variant chr21-45986507-G-A is described in ClinVar as Benign. ClinVar VariationId is 93876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3 link	c.429-19G>A		intron_variant	Intron 3 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.429-19G>A		intron_variant	Intron 3 of 34	1	NM_001848.3	ENSP00000355180.3		P12109

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28093

AN:

151974

Hom.:

3055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.206

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.00830

Gnomad SAS

AF:

0.0966

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.178

GnomAD2 exomes

AF:

0.182

AC:

29123

AN:

159964

AF XY:

0.180

show subpopulations

Gnomad AFR exome

AF:

0.0976

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.00567

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.228

AC:

319313

AN:

1399796

Hom.:

39057

Cov.:

AF XY:

0.224

AC XY:

154871

AN XY:

690758

show subpopulations

African (AFR)

AF:

0.0981

AC:

3110

AN:

31700

American (AMR)

AF:

0.159

AC:

5766

AN:

36156

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4253

AN:

25214

East Asian (EAS)

AF:

0.00618

AC:

222

AN:

35914

South Asian (SAS)

AF:

0.110

AC:

8745

AN:

79348

European-Finnish (FIN)

AF:

0.265

AC:

12774

AN:

48138

Middle Eastern (MID)

AF:

0.131

AC:

745

AN:

5686

European-Non Finnish (NFE)

AF:

0.252

AC:

271825

AN:

1079552

Other (OTH)

AF:

0.204

AC:

11873

AN:

58088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

11754

23508

35261

47015

58769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9114

18228

27342

36456

45570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.185

AC:

28105

AN:

152092

Hom.:

3057

Cov.:

AF XY:

0.184

AC XY:

13691

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.102

AC:

4230

AN:

41518

American (AMR)

AF:

0.186

AC:

2844

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

592

AN:

3472

East Asian (EAS)

AF:

0.00871

AC:

AN:

5168

South Asian (SAS)

AF:

0.0975

AC:

469

AN:

4812

European-Finnish (FIN)

AF:

0.272

AC:

2872

AN:

10578

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16463

AN:

67954

Other (OTH)

AF:

0.176

AC:

373

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1131

2261

3392

4522

5653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.133

Hom.:

373

Bravo

AF:

0.176

Asia WGS

AF:

0.0540

AC:

190

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jul 09, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 05, 2016

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Bethlem myopathy 1A

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.054

(source)

DANN

Benign

0.59

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over