11-47349933-AGG-AG

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000256.3(MYBPC3):c.506-12delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 30296 hom., cov: 0)

Exomes 𝑓: 0.70 ( 352985 hom. )

Consequence

MYBPC3
NM_000256.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:18

Conservation

PhyloP100: 0.0850

Publications

11 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 -16 ACMG points.

BP6

Variant 11-47349933-AG-A is Benign according to our data. Variant chr11-47349933-AG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 42763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000256.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC3	NM_000256.3	MANE Select	c.506-12delC		intron	N/A	NP_000247.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYBPC3	ENST00000545968.6	TSL:5 MANE Select	c.506-12delC	intron	N/A	ENSP00000442795.1
MYBPC3	ENST00000399249.6	TSL:5	c.506-12delC	intron	N/A	ENSP00000382193.2
MYBPC3	ENST00000544791.1	TSL:5	n.506-12delC	intron	N/A	ENSP00000444259.1

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93300

AN:

151942

Hom.:

30276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.863

Gnomad AMR

AF:

0.660

Gnomad ASJ

AF:

0.721

Gnomad EAS

AF:

0.648

Gnomad SAS

AF:

0.728

Gnomad FIN

AF:

0.604

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.678

GnomAD2 exomes

AF:

0.665

AC:

135009

AN:

202962

AF XY:

0.676

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.596

Gnomad ASJ exome

AF:

0.727

Gnomad EAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.616

Gnomad NFE exome

AF:

0.717

Gnomad OTH exome

AF:

0.716

GnomAD4 exome

AF:

0.698

AC:

1001523

AN:

1434702

Hom.:

352985

Cov.:

AF XY:

0.700

AC XY:

497885

AN XY:

711092

show subpopulations

African (AFR)

AF:

0.383

AC:

12604

AN:

32910

American (AMR)

AF:

0.603

AC:

24538

AN:

40662

Ashkenazi Jewish (ASJ)

AF:

0.725

AC:

18553

AN:

25584

East Asian (EAS)

AF:

0.577

AC:

22066

AN:

38222

South Asian (SAS)

AF:

0.709

AC:

58419

AN:

82350

European-Finnish (FIN)

AF:

0.622

AC:

31909

AN:

51288

Middle Eastern (MID)

AF:

0.728

AC:

4121

AN:

5658

European-Non Finnish (NFE)

AF:

0.717

AC:

787620

AN:

1098642

Other (OTH)

AF:

0.702

AC:

41693

AN:

59386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

18211

36422

54632

72843

91054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19618

39236

58854

78472

98090

<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:

0.614

AC:

93369

AN:

152060

Hom.:

30296

Cov.:

AF XY:

0.612

AC XY:

45467

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.390

AC:

16192

AN:

41472

American (AMR)

AF:

0.660

AC:

10094

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.721

AC:

2502

AN:

3472

East Asian (EAS)

AF:

0.647

AC:

3335

AN:

5152

South Asian (SAS)

AF:

0.728

AC:

3516

AN:

4828

European-Finnish (FIN)

AF:

0.604

AC:

6374

AN:

10548

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.720

AC:

48921

AN:

67974

Other (OTH)

AF:

0.682

AC:

1442

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1695

3390

5084

6779

8474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

764

1528

2292

3056

3820

<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:

0.687

Hom.:

6634

Bravo

AF:

0.607

Asia WGS

AF:

0.709

AC:

2467

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:18

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 20, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BA1

Feb 05, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hypertrophic cardiomyopathy 4

Benign:4

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Sep 21, 2015

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Cardiomyopathy

Benign:2

Apr 08, 2018

Color Diagnostics, LLC DBA Color Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Oct 10, 2022

Cohesion Phenomics

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Jun 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 32841044)

Nov 21, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hypertrophic cardiomyopathy

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

Left ventricular noncompaction cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.085

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over