21-45986696-GC-GCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001848.3(COL6A1):c.588+19dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,544,256 control chromosomes in the GnomAD database, including 3,907 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 1493 hom., cov: 31)

Exomes 𝑓: 0.024 ( 2414 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.45

Publications

2 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 -16 ACMG points.

BP6

Variant 21-45986696-G-GC is Benign according to our data. Variant chr21-45986696-G-GC is described in ClinVar as Benign. ClinVar VariationId is 93880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3 link	c.588+19dupC		intron_variant	Intron 4 of 34	ENST00000361866.8	NP_001839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8 link	c.588+11_588+12insC		intron_variant	Intron 4 of 34	1	NM_001848.3	ENSP00000355180.3

Frequencies

GnomAD3 genomes

AF:

0.0857

AC:

12998

AN:

151632

Hom.:

1492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0428

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.0993

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00709

Gnomad OTH

AF:

0.0570

GnomAD2 exomes

AF:

0.0478

AC:

7173

AN:

150210

AF XY:

0.0483

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.0265

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.00317

Gnomad NFE exome

AF:

0.00708

Gnomad OTH exome

AF:

0.0293

GnomAD4 exome

AF:

0.0239

AC:

33290

AN:

1392506

Hom.:

2414

Cov.:

AF XY:

0.0254

AC XY:

17462

AN XY:

686934

show subpopulations

African (AFR)

AF:

0.266

AC:

8374

AN:

31432

American (AMR)

AF:

0.0290

AC:

1037

AN:

35746

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

471

AN:

25172

East Asian (EAS)

AF:

0.187

AC:

6676

AN:

35692

South Asian (SAS)

AF:

0.100

AC:

7938

AN:

79144

European-Finnish (FIN)

AF:

0.00351

AC:

154

AN:

43914

Middle Eastern (MID)

AF:

0.0402

AC:

210

AN:

5228

European-Non Finnish (NFE)

AF:

0.00585

AC:

6309

AN:

1078336

Other (OTH)

AF:

0.0367

AC:

2121

AN:

57842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

1734

3468

5202

6936

8670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.0858

AC:

13015

AN:

151750

Hom.:

1493

Cov.:

AF XY:

0.0859

AC XY:

6372

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.254

AC:

10469

AN:

41268

American (AMR)

AF:

0.0428

AC:

654

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3470

East Asian (EAS)

AF:

0.142

AC:

721

AN:

5072

South Asian (SAS)

AF:

0.100

AC:

479

AN:

4790

European-Finnish (FIN)

AF:

0.00264

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00708

AC:

481

AN:

67952

Other (OTH)

AF:

0.0560

AC:

118

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

427

854

1280

1707

2134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.00958

Hom.:

Bravo

AF:

0.0944

Asia WGS

AF:

0.100

AC:

345

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

- -

Sep 05, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 02, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

Collagen 6-related myopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.5

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