rs71324475

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.428+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,590,536 control chromosomes in the GnomAD database, including 4,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 248 hom., cov: 35)

Exomes 𝑓: 0.069 ( 3938 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.858

Publications

4 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=-0.92).

BP6

Variant 21-45984509-G-A is Benign according to our data. Variant chr21-45984509-G-A is described in ClinVar as Benign. ClinVar VariationId is 93875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3 link	c.428+40G>A		intron_variant	Intron 3 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.428+40G>A		intron_variant	Intron 3 of 34	1	NM_001848.3	ENSP00000355180.3

Frequencies

GnomAD3 genomes

AF:

0.0496

AC:

7553

AN:

152228

Hom.:

248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0486

Gnomad ASJ

AF:

0.0645

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0169

Gnomad FIN

AF:

0.0417

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0781

Gnomad OTH

AF:

0.0525

GnomAD2 exomes

AF:

0.0478

AC:

11146

AN:

232960

AF XY:

0.0481

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.0262

Gnomad ASJ exome

AF:

0.0597

Gnomad EAS exome

AF:

0.0000559

Gnomad FIN exome

AF:

0.0422

Gnomad NFE exome

AF:

0.0754

Gnomad OTH exome

AF:

0.0559

GnomAD4 exome

AF:

0.0692

AC:

99541

AN:

1438190

Hom.:

3938

Cov.:

AF XY:

0.0679

AC XY:

48622

AN XY:

716550

show subpopulations

African (AFR)

AF:

0.0114

AC:

377

AN:

33180

American (AMR)

AF:

0.0277

AC:

1235

AN:

44574

Ashkenazi Jewish (ASJ)

AF:

0.0614

AC:

1597

AN:

26018

East Asian (EAS)

AF:

0.000152

AC:

AN:

39522

South Asian (SAS)

AF:

0.0185

AC:

1586

AN:

85714

European-Finnish (FIN)

AF:

0.0457

AC:

1909

AN:

41758

Middle Eastern (MID)

AF:

0.0396

AC:

227

AN:

5736

European-Non Finnish (NFE)

AF:

0.0810

AC:

89241

AN:

1101876

Other (OTH)

AF:

0.0562

AC:

3363

AN:

59812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

4892

9783

14675

19566

24458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3212

6424

9636

12848

16060

<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:

0.0495

AC:

7548

AN:

152346

Hom.:

248

Cov.:

AF XY:

0.0465

AC XY:

3461

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0146

AC:

607

AN:

41590

American (AMR)

AF:

0.0486

AC:

743

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0645

AC:

224

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.0168

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0417

AC:

443

AN:

10626

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0780

AC:

5308

AN:

68014

Other (OTH)

AF:

0.0520

AC:

110

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

380

760

1141

1521

1901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0625

Hom.:

120

Bravo

AF:

0.0483

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 28, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jul 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.92

CADD

Benign

0.19

(source)

DANN

Benign

0.60

PhyloP100

-0.86

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