rs2856650

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_000256.3(MYBPC3):c.1091-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,579,618 control chromosomes in the GnomAD database, including 69,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5253 hom., cov: 28)

Exomes 𝑓: 0.30 ( 64496 hom. )

Consequence

MYBPC3
NM_000256.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.102

Publications

25 publications found

Variant links:

Genes affected

MYBPC3 (HGNC:7551): (myosin binding protein C3) MYBPC3 encodes the cardiac isoform of myosin-binding protein C. Myosin-binding protein C is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. MYBPC3 is expressed exclusively in heart muscle and is a key regulator of cardiac contraction. Mutations in this gene are a frequent cause of familial hypertrophic cardiomyopathy. [provided by RefSeq, May 2022]

MYBPC3 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 4
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
left ventricular noncompaction 10
Inheritance: AR, AD Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
atrial fibrillation
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

MYBPC3 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 11-47343648-G-A is Benign according to our data. Variant chr11-47343648-G-A is described in ClinVar as Benign. ClinVar VariationId is 188541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3 link	c.1091-24C>T		intron_variant	Intron 12 of 34	ENST00000545968.6	NP_000247.2	Q14896-1A5YM48

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYBPC3	ENST00000545968.6 link	c.1091-24C>T	intron_variant	Intron 12 of 34	5	NM_000256.3	ENSP00000442795.1	Q14896-1
MYBPC3	ENST00000399249.6 link	c.1091-24C>T	intron_variant	Intron 11 of 33	5		ENSP00000382193.2	A8MXZ9
MYBPC3	ENST00000544791.1 link	n.1091-24C>T	intron_variant	Intron 12 of 26	5		ENSP00000444259.1	F5GZR4

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

36879

AN:

150506

Hom.:

5242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0888

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.298

GnomAD2 exomes

AF:

0.298

AC:

64539

AN:

216904

AF XY:

0.300

show subpopulations

Gnomad AFR exome

AF:

0.0835

Gnomad AMR exome

AF:

0.369

Gnomad ASJ exome

AF:

0.351

Gnomad EAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.247

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.296

AC:

423377

AN:

1428990

Hom.:

64496

Cov.:

AF XY:

0.297

AC XY:

210289

AN XY:

707552

show subpopulations

African (AFR)

AF:

0.0849

AC:

2813

AN:

33128

American (AMR)

AF:

0.372

AC:

15886

AN:

42754

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

8618

AN:

24752

East Asian (EAS)

AF:

0.326

AC:

12695

AN:

38994

South Asian (SAS)

AF:

0.296

AC:

24503

AN:

82648

European-Finnish (FIN)

AF:

0.250

AC:

11558

AN:

46210

Middle Eastern (MID)

AF:

0.330

AC:

1698

AN:

5144

European-Non Finnish (NFE)

AF:

0.299

AC:

327916

AN:

1096262

Other (OTH)

AF:

0.299

AC:

17690

AN:

59098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

13674

27349

41023

54698

68372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10906

21812

32718

43624

54530

<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:

0.245

AC:

36903

AN:

150628

Hom.:

5253

Cov.:

AF XY:

0.245

AC XY:

17995

AN XY:

73450

show subpopulations

African (AFR)

AF:

0.0887

AC:

3655

AN:

41216

American (AMR)

AF:

0.361

AC:

5407

AN:

14998

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1195

AN:

3456

East Asian (EAS)

AF:

0.295

AC:

1477

AN:

5008

South Asian (SAS)

AF:

0.300

AC:

1418

AN:

4720

European-Finnish (FIN)

AF:

0.228

AC:

2372

AN:

10388

Middle Eastern (MID)

AF:

0.352

AC:

102

AN:

290

European-Non Finnish (NFE)

AF:

0.299

AC:

20222

AN:

67566

Other (OTH)

AF:

0.304

AC:

635

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1147

2294

3442

4589

5736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.266

Hom.:

4107

Bravo

AF:

0.252

Asia WGS

AF:

0.305

AC:

1059

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Left ventricular noncompaction 10

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy 4

Benign:1

Sep 05, 2021

Genome-Nilou Lab

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

-0.85

CADD

Benign

2.8

(source)

DANN

Benign

0.62

PhyloP100

-0.10

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