11-47349056-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000256.3(MYBPC3):c.655-515A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 150,140 control chromosomes in the GnomAD database, including 23,003 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (23003 hom., cov: 25)
• Consequence: MYBPC3 NM_000256.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPC3	NM_000256.3	c.655-515A>G		intron_variant		ENST00000545968.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC3	ENST00000545968.6	c.655-515A>G		intron_variant		5	NM_000256.3	P4
MYBPC3	ENST00000399249.6	c.655-515A>G		intron_variant		5		A2
MYBPC3	ENST00000544791.1	c.655-515A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.521 AC: 78158 AN: 150022 Hom.: 22996 Cov.: 25

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.576

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.521 AC: 78180 AN: 150140 Hom.: 23003 Cov.: 25 AF XY: 0.516 AC XY: 37836 AN XY: 73270

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.580

Alfa AF: 0.639 Hom.: 43130

Bravo AF: 0.512

Asia WGS AF: 0.496 AC: 1726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.5
Dann	Benign	0.70

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: rs2697920; hg19: chr11-47370607;