rs11553519

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.347G>A(p.Ser116Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 1,612,750 control chromosomes in the GnomAD database, including 1,767 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S116S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.045 ( 165 hom., cov: 35)

Exomes 𝑓: 0.044 ( 1602 hom. )

Consequence

COL6A1
NM_001848.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.897

Publications

26 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 (MetaRNN=0.002249211).

BP6

Variant 21-45984388-G-A is Benign according to our data. Variant chr21-45984388-G-A is described in ClinVar as Benign. ClinVar VariationId is 93872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3 link	c.347G>A	p.Ser116Asn	missense_variant	Exon 3 of 35	ENST00000361866.8	NP_001839.2	P12109A0A384P5H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8 link	c.347G>A	p.Ser116Asn	missense_variant	Exon 3 of 35	1	NM_001848.3	ENSP00000355180.3		P12109

Frequencies

GnomAD3 genomes

AF:

0.0455

AC:

6926

AN:

152264

Hom.:

165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0362

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0319

Gnomad ASJ

AF:

0.0446

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.0322

Gnomad FIN

AF:

0.0752

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0541

Gnomad OTH

AF:

0.0468

GnomAD2 exomes

AF:

0.0424

AC:

10584

AN:

249534

AF XY:

0.0432

show subpopulations

Gnomad AFR exome

AF:

0.0338

Gnomad AMR exome

AF:

0.0243

Gnomad ASJ exome

AF:

0.0447

Gnomad EAS exome

AF:

0.00256

Gnomad FIN exome

AF:

0.0744

Gnomad NFE exome

AF:

0.0523

Gnomad OTH exome

AF:

0.0519

GnomAD4 exome

AF:

0.0443

AC:

64674

AN:

1460368

Hom.:

1602

Cov.:

AF XY:

0.0442

AC XY:

32081

AN XY:

726490

show subpopulations

African (AFR)

AF:

0.0332

AC:

1111

AN:

33476

American (AMR)

AF:

0.0254

AC:

1136

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0451

AC:

1177

AN:

26124

East Asian (EAS)

AF:

0.00353

AC:

140

AN:

39694

South Asian (SAS)

AF:

0.0287

AC:

2478

AN:

86254

European-Finnish (FIN)

AF:

0.0747

AC:

3889

AN:

52048

Middle Eastern (MID)

AF:

0.0721

AC:

416

AN:

5768

European-Non Finnish (NFE)

AF:

0.0465

AC:

51715

AN:

1111922

Other (OTH)

AF:

0.0433

AC:

2612

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4086

8172

12259

16345

20431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1786

3572

5358

7144

8930

<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:

0.0455

AC:

6927

AN:

152382

Hom.:

165

Cov.:

AF XY:

0.0447

AC XY:

3330

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.0361

AC:

1501

AN:

41590

American (AMR)

AF:

0.0317

AC:

486

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0446

AC:

155

AN:

3472

East Asian (EAS)

AF:

0.00270

AC:

AN:

5186

South Asian (SAS)

AF:

0.0323

AC:

156

AN:

4834

European-Finnish (FIN)

AF:

0.0752

AC:

799

AN:

10632

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0541

AC:

3684

AN:

68036

Other (OTH)

AF:

0.0473

AC:

100

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

353

706

1059

1412

1765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0467

Hom.:

336

Bravo

AF:

0.0402

TwinsUK

AF:

0.0399

AC:

148

ALSPAC

AF:

0.0418

AC:

161

ESP6500AA

AF:

0.0284

AC:

125

ESP6500EA

AF:

0.0472

AC:

406

ExAC

AF:

0.0427

AC:

5168

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0511

EpiControl

AF:

0.0486

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:11

Aug 28, 2012

Eurofins Ntd Llc (ga)

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 12, 2023

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 531/13002=4% -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 11, 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. -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Collagen 6-related myopathy

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Bethlem myopathy 1A

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.6

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.52

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.40

N;.

PhyloP100

0.90

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.67

N;.

REVEL

Benign

0.19

Sift

Benign

0.51

T;.

Sift4G

Benign

0.35

T;T

Polyphen

0.14

B;.

Vest4

0.15

MPC

0.21

ClinPred

0.0054

GERP RS

1.4

Varity_R

0.049

gMVP

0.69

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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