21-46001950-C-T

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.1957-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,609,230 control chromosomes in the GnomAD database, including 80,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7478 hom., cov: 33)

Exomes 𝑓: 0.30 ( 72705 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Splicing: ADA: 0.00001753

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0250

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 21-46001950-C-T is Benign according to our data. Variant chr21-46001950-C-T is described in ClinVar as Benign. ClinVar VariationId is 93842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 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.1957-11C>T		intron	N/A	NP_001839.2	P12109

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL6A1	ENST00000361866.8	TSL:1 MANE Select	c.1957-11C>T	intron	N/A	ENSP00000355180.3	P12109
COL6A1	ENST00000498614.5	TSL:1	n.191-11C>T	intron	N/A
COL6A1	ENST00000866134.1		c.565-577C>T	intron	N/A	ENSP00000536193.1

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44817

AN:

151902

Hom.:

7467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.636

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.288

Gnomad OTH

AF:

0.313

GnomAD2 exomes

AF:

0.364

AC:

86718

AN:

238236

AF XY:

0.359

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.514

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.637

Gnomad FIN exome

AF:

0.354

Gnomad NFE exome

AF:

0.293

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.305

AC:

444424

AN:

1457210

Hom.:

72705

Cov.:

AF XY:

0.307

AC XY:

222831

AN XY:

724804

show subpopulations

African (AFR)

AF:

0.173

AC:

5802

AN:

33450

American (AMR)

AF:

0.504

AC:

22347

AN:

44362

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

9495

AN:

26036

East Asian (EAS)

AF:

0.622

AC:

24637

AN:

39586

South Asian (SAS)

AF:

0.377

AC:

32346

AN:

85844

European-Finnish (FIN)

AF:

0.358

AC:

18505

AN:

51644

Middle Eastern (MID)

AF:

0.365

AC:

2103

AN:

5758

European-Non Finnish (NFE)

AF:

0.279

AC:

309662

AN:

1110298

Other (OTH)

AF:

0.324

AC:

19527

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

16650

33299

49949

66598

83248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10444

20888

31332

41776

52220

<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:

0.295

AC:

44843

AN:

152020

Hom.:

7478

Cov.:

AF XY:

0.302

AC XY:

22464

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.184

AC:

7641

AN:

41484

American (AMR)

AF:

0.409

AC:

6249

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1279

AN:

3472

East Asian (EAS)

AF:

0.637

AC:

3282

AN:

5156

South Asian (SAS)

AF:

0.393

AC:

1895

AN:

4816

European-Finnish (FIN)

AF:

0.358

AC:

3786

AN:

10568

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.288

AC:

19574

AN:

67940

Other (OTH)

AF:

0.317

AC:

668

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1542

3085

4627

6170

7712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.306

Hom.:

1411

Bravo

AF:

0.294

Asia WGS

AF:

0.496

AC:

1723

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Bethlem myopathy 1A (1)

Collagen 6-related myopathy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.0

(source)

DANN

Benign

0.49

PhyloP100

0.025

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0

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