rs35796750

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2251-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,613,216 control chromosomes in the GnomAD database, including 244,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20674 hom., cov: 34)

Exomes 𝑓: 0.55 ( 224134 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.390

Publications

21 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:

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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=-0.84).

BP6

Variant 21-46002498-C-T is Benign according to our data. Variant chr21-46002498-C-T is described in ClinVar as Benign. ClinVar VariationId is 93850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 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.2251-29C>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.2251-29C>T	intron	N/A	ENSP00000355180.3	P12109
COL6A1	ENST00000498614.5	TSL:1	n.485-29C>T	intron	N/A
COL6A1	ENST00000866134.1		c.565-29C>T	intron	N/A	ENSP00000536193.1

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77812

AN:

152036

Hom.:

20664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.647

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.713

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.510

GnomAD2 exomes

AF:

0.568

AC:

142177

AN:

250474

AF XY:

0.569

show subpopulations

Gnomad AFR exome

AF:

0.366

Gnomad AMR exome

AF:

0.618

Gnomad ASJ exome

AF:

0.584

Gnomad EAS exome

AF:

0.713

Gnomad FIN exome

AF:

0.605

Gnomad NFE exome

AF:

0.551

Gnomad OTH exome

AF:

0.579

GnomAD4 exome

AF:

0.552

AC:

806252

AN:

1461062

Hom.:

224134

Cov.:

AF XY:

0.553

AC XY:

401813

AN XY:

726878

show subpopulations

African (AFR)

AF:

0.360

AC:

12047

AN:

33466

American (AMR)

AF:

0.614

AC:

27453

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.576

AC:

15058

AN:

26130

East Asian (EAS)

AF:

0.690

AC:

27406

AN:

39692

South Asian (SAS)

AF:

0.556

AC:

47960

AN:

86242

European-Finnish (FIN)

AF:

0.611

AC:

32547

AN:

53242

Middle Eastern (MID)

AF:

0.525

AC:

3029

AN:

5766

European-Non Finnish (NFE)

AF:

0.546

AC:

607224

AN:

1111444

Other (OTH)

AF:

0.555

AC:

33528

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

22501

45001

67502

90002

112503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17122

34244

51366

68488

85610

<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:

0.512

AC:

77846

AN:

152154

Hom.:

20674

Cov.:

AF XY:

0.514

AC XY:

38273

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.366

AC:

15194

AN:

41524

American (AMR)

AF:

0.560

AC:

8579

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

1980

AN:

3468

East Asian (EAS)

AF:

0.712

AC:

3660

AN:

5140

South Asian (SAS)

AF:

0.567

AC:

2739

AN:

4828

European-Finnish (FIN)

AF:

0.602

AC:

6383

AN:

10604

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.552

AC:

37495

AN:

67964

Other (OTH)

AF:

0.513

AC:

1083

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1986

3971

5957

7942

9928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.539

Hom.:

4132

Bravo

AF:

0.501

Asia WGS

AF:

0.623

AC:

2165

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.7

(source)

DANN

Benign

0.74

PhyloP100

-0.39

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