rs3729948

Variant names:

Variant summary

Our verdict is The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_000256.3(MYBPC3):c.2308+18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0428 (AC=69,037) in the gnomAD database across 1,613,746 control chromosomes, including 1,960 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.111. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★). The variant has been observed in cBioPortal in 1 sample across 1 study and 1 cancer type; somatic enrichment level: NONE (Observed in at most one deduplicated cBioPortal case.).

Frequency

Genomes: 𝑓 0.051 ( 265 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1695 hom. )

Consequence

MYBPC3
NM_000256.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.644

Publications

9 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
left ventricular noncompaction 10
Inheritance: AD, AR 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, G2P
atrial fibrillation
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
dilated cardiomyopathy
Inheritance: AD, AR Classification: LIMITED Submitted by: ClinGen
familial dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: G2P

MYBPC3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000256.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Specifications for MYBPC3 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 points.

GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.111 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC3	NM_000256.3	MANE Select	c.2308+18C>G		intron	N/A	NP_000247.2	Q14896-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYBPC3	ENST00000545968.6	TSL:5 MANE Select	c.2308+18C>G	intron	N/A	ENSP00000442795.1	Q14896-1
MYBPC3	ENST00000399249.6	TSL:5	c.2308+18C>G	intron	N/A	ENSP00000382193.2	A8MXZ9
MYBPC3	ENST00000544791.1	TSL:5	n.2308+18C>G	intron	N/A	ENSP00000444259.1	F5GZR4

Frequencies

GnomAD3 genomes

AF:

0.0508

AC:

7736

AN:

152156

Hom.:

266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0803

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0228

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.0433

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0465

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0382

Gnomad OTH

AF:

0.0445

GnomAD2 exomes

AF:

0.0483

AC:

12007

AN:

248776

AF XY:

0.0515

show subpopulations

Gnomad AFR exome

AF:

0.0826

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0125

Gnomad EAS exome

AF:

0.0381

Gnomad FIN exome

AF:

0.0499

Gnomad NFE exome

AF:

0.0392

Gnomad OTH exome

AF:

0.0361

GnomAD4 exome

AF:

0.0419

AC:

61298

AN:

1461472

Hom.:

1695

Cov.:

AF XY:

0.0441

AC XY:

32047

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.0843

AC:

2821

AN:

33478

American (AMR)

AF:

0.0170

AC:

762

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0126

AC:

330

AN:

26134

East Asian (EAS)

AF:

0.0353

AC:

1402

AN:

39696

South Asian (SAS)

AF:

0.112

AC:

9693

AN:

86238

European-Finnish (FIN)

AF:

0.0501

AC:

2670

AN:

53308

Middle Eastern (MID)

AF:

0.0319

AC:

184

AN:

5764

European-Non Finnish (NFE)

AF:

0.0366

AC:

40691

AN:

1111778

Other (OTH)

AF:

0.0455

AC:

2745

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

2921

5843

8764

11686

14607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1534

3068

4602

6136

7670

<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:

0.0508

AC:

7739

AN:

152274

Hom.:

265

Cov.:

AF XY:

0.0513

AC XY:

3816

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0804

AC:

3341

AN:

41542

American (AMR)

AF:

0.0227

AC:

348

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3470

East Asian (EAS)

AF:

0.0426

AC:

221

AN:

5182

South Asian (SAS)

AF:

0.118

AC:

567

AN:

4822

European-Finnish (FIN)

AF:

0.0465

AC:

494

AN:

10616

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0381

AC:

2595

AN:

68022

Other (OTH)

AF:

0.0445

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

374

748

1123

1497

1871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0435

Hom.:

Bravo

AF:

0.0481

Asia WGS

AF:

0.119

AC:

413

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0339

AC:

4140

AN:

122174

Turkish Variome

AF:

0.0368

AC:

247

AN:

6714

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.0365

AC:

327

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.0418

AC:

AN:

2342

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Hypertrophic cardiomyopathy 4 (3)

Hypertrophic cardiomyopathy (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.0

(source)

DANN

Benign

0.57

PhyloP100

0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over