rs74982956

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.1119+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00903 in 1,606,404 control chromosomes in the GnomAD database, including 899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 76 hom., cov: 33)

Exomes 𝑓: 0.0091 ( 823 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.33

Publications

1 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=-0.86).

BP6

Variant 21-45991080-C-T is Benign according to our data. Variant chr21-45991080-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3 link	c.1119+39C>T		intron_variant	Intron 15 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.1119+39C>T		intron_variant	Intron 15 of 34	1	NM_001848.3	ENSP00000355180.3		P12109

Frequencies

GnomAD3 genomes

AF:

0.00852

AC:

1297

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.0429

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.0183

AC:

4525

AN:

247546

AF XY:

0.0185

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.00542

Gnomad EAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.00269

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.0117

GnomAD4 exome

AF:

0.00909

AC:

13215

AN:

1454102

Hom.:

823

Cov.:

AF XY:

0.00991

AC XY:

7174

AN XY:

723736

show subpopulations

African (AFR)

AF:

0.000511

AC:

AN:

33286

American (AMR)

AF:

0.0116

AC:

520

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.00606

AC:

158

AN:

26090

East Asian (EAS)

AF:

0.182

AC:

7208

AN:

39660

South Asian (SAS)

AF:

0.0423

AC:

3646

AN:

86130

European-Finnish (FIN)

AF:

0.00279

AC:

146

AN:

52318

Middle Eastern (MID)

AF:

0.0104

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000702

AC:

777

AN:

1106056

Other (OTH)

AF:

0.0114

AC:

683

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

663

1326

1989

2652

3315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<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:

0.00850

AC:

1295

AN:

152302

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

770

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41562

American (AMR)

AF:

0.0129

AC:

198

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00662

AC:

AN:

3472

East Asian (EAS)

AF:

0.146

AC:

756

AN:

5162

South Asian (SAS)

AF:

0.0427

AC:

206

AN:

4822

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000735

AC:

AN:

68036

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

122

182

243

304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00315

Hom.:

Bravo

AF:

0.00905

Asia WGS

AF:

0.0690

AC:

238

AN:

3478

ClinVar

Significance: Benign/Likely 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:Likely 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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 29, 2018

GeneDx

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

-0.86

CADD

Benign

1.9

(source)

DANN

Benign

0.68

PhyloP100

-3.3

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