rs1053315

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001848.3(COL6A1):c.2667G>A(p.Ala889Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,612,626 control chromosomes in the GnomAD database, including 75,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8043 hom., cov: 35)

Exomes 𝑓: 0.30 ( 67749 hom. )

Consequence

COL6A1
NM_001848.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -1.28

Publications

19 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):

Bethlem myopathy 1A
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P
collagen 6-related myopathy
Inheritance: SD, AD, AR Classification: DEFINITIVE Submitted by: ClinGen
Ullrich congenital muscular dystrophy 1A
Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 21-46003593-G-A is Benign according to our data. Variant chr21-46003593-G-A is described in ClinVar as Benign. ClinVar VariationId is 93864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001848.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A1	NM_001848.3	MANE Select	c.2667G>A	p.Ala889Ala	synonymous	Exon 35 of 35	NP_001839.2	P12109

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL6A1	ENST00000361866.8	TSL:1 MANE Select	c.2667G>A	p.Ala889Ala	synonymous	Exon 35 of 35	ENSP00000355180.3	P12109
COL6A1	ENST00000498614.5	TSL:1	n.901G>A		non_coding_transcript_exon	Exon 6 of 6
COL6A1	ENST00000866134.1		c.981G>A	p.Ala327Ala	synonymous	Exon 7 of 7	ENSP00000536193.1

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48515

AN:

152068

Hom.:

8036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.296

GnomAD2 exomes

AF:

0.282

AC:

69549

AN:

246606

AF XY:

0.277

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.305

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.301

AC:

440268

AN:

1460440

Hom.:

67749

Cov.:

AF XY:

0.298

AC XY:

216630

AN XY:

726564

show subpopulations

African (AFR)

AF:

0.402

AC:

13447

AN:

33470

American (AMR)

AF:

0.297

AC:

13294

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

6079

AN:

26112

East Asian (EAS)

AF:

0.189

AC:

7510

AN:

39688

South Asian (SAS)

AF:

0.232

AC:

19979

AN:

86252

European-Finnish (FIN)

AF:

0.272

AC:

14233

AN:

52288

Middle Eastern (MID)

AF:

0.248

AC:

1433

AN:

5768

European-Non Finnish (NFE)

AF:

0.312

AC:

347246

AN:

1111798

Other (OTH)

AF:

0.282

AC:

17047

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

20732

41464

62197

82929

103661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11342

22684

34026

45368

56710

<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:

0.319

AC:

48553

AN:

152186

Hom.:

8043

Cov.:

AF XY:

0.318

AC XY:

23631

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.398

AC:

16513

AN:

41530

American (AMR)

AF:

0.322

AC:

4926

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

798

AN:

3468

East Asian (EAS)

AF:

0.162

AC:

835

AN:

5162

South Asian (SAS)

AF:

0.220

AC:

1061

AN:

4828

European-Finnish (FIN)

AF:

0.277

AC:

2935

AN:

10600

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20640

AN:

67980

Other (OTH)

AF:

0.292

AC:

618

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1763

3526

5289

7052

8815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<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:

0.308

Hom.:

3151

Bravo

AF:

0.327

Asia WGS

AF:

0.178

AC:

622

AN:

3478

EpiCase

AF:

0.305

EpiControl

AF:

0.299

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (8)

Bethlem myopathy 1A (2)

Collagen 6-related myopathy (1)

not provided (1)

Ullrich congenital muscular dystrophy 1A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.38

(source)

DANN

Benign

0.62

PhyloP100

-1.3

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over