dbSNP rs3729948: MYBPC3:c.2308+18C>G (chr11-47338502-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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 frequency of 0.0428 in 1,613,746 control chromosomes in the GnomAD database, including 1,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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:10

Conservation

PhyloP100: 0.644

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-47338502-G-C is Benign according to our data. Variant chr11-47338502-G-C is described in ClinVar as [Benign]. Clinvar id is 188566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47338502-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3 link	c.2308+18C>G		intron_variant	Intron 23 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.2308+18C>G	intron_variant	Intron 23 of 34	5	NM_000256.3	ENSP00000442795.1	Q14896-1
MYBPC3	ENST00000399249.6 link	c.2308+18C>G	intron_variant	Intron 22 of 33	5		ENSP00000382193.2	A8MXZ9
MYBPC3	ENST00000544791.1 link	n.2308+18C>G	intron_variant	Intron 23 of 26	5		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

GnomAD3 exomes

AF:

0.0483

AC:

12007

AN:

248776

Hom.:

458

AF XY:

0.0515

AC XY:

6957

AN XY:

134972

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 SAS exome

AF:

0.120

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

Gnomad4 AFR exome

AF:

0.0843

Gnomad4 AMR exome

AF:

0.0170

Gnomad4 ASJ exome

AF:

0.0126

Gnomad4 EAS exome

AF:

0.0353

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0501

Gnomad4 NFE exome

AF:

0.0366

Gnomad4 OTH exome

AF:

0.0455

GnomAD4 genome

AF:

0.0508

AC:

7739

AN:

152274

Hom.:

265

Cov.:

AF XY:

0.0513

AC XY:

3816

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0804

Gnomad4 AMR

AF:

0.0227

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.0426

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0465

Gnomad4 NFE

AF:

0.0381

Gnomad4 OTH

AF:

0.0445

Alfa

AF:

0.0435

Hom.:

Bravo

AF:

0.0481

Asia WGS

AF:

0.119

AC:

413

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

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

- -

Clinical Genetics, Academic Medical Center

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

- -

Hypertrophic cardiomyopathy 4

Benign:3

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

- -

Jul 28, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

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

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hypertrophic cardiomyopathy

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.0

DANN

Benign

0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over