11-47349933-AGG-AG

Position:

• chr11-47349933-AGG-AG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000256.3(MYBPC3):​c.506-12del variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:17
• Conservation: PhyloP100: 0.0850

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 42763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47349933-AG-A is described in Lovd as [Benign]. Variant chr11-47349933-AG-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC3	NM_000256.3	c.506-12del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000545968.6	NP_000247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6	c.506-12del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_000256.3	ENSP00000442795	P4
MYBPC3	ENST00000399249.6	c.506-12del		splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000382193	A2
MYBPC3	ENST00000544791.1	c.506-12del		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000444259

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93300 AN: 151942 Hom.: 30276 Cov.: 0

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

GnomAD3 exomes AF: 0.665 AC: 135009 AN: 202962 Hom.: 45716 AF XY: 0.676 AC XY: 74374 AN XY: 110010

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 SAS exome AF: 0.714

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.: 0 AF XY: 0.700 AC XY: 497885 AN XY: 711092

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.725

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.709

Gnomad4 FIN exome AF: 0.622

Gnomad4 NFE exome AF: 0.717

Gnomad4 OTH exome AF: 0.702

GnomAD4 genome AF: 0.614 AC: 93369 AN: 152060 Hom.: 30296 Cov.: 0 AF XY: 0.612 AC XY: 45467 AN XY: 74324

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.682

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:17

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 05, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jul 20, 2011	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Hypertrophic cardiomyopathy 4 Benign:4

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -

Cardiomyopathy Benign:2

Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Apr 08, 2018	- -
Benign, no assertion criteria provided	clinical testing	Cohesion Phenomics	Oct 10, 2022	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2018	This variant is associated with the following publications: (PMID: 32841044) -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Hypertrophic cardiomyopathy Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Left ventricular noncompaction 10 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Left ventricular noncompaction cardiomyopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs11570050; hg19: chr11-47371484;