rs2856653

Positions:

• chr11-47339533-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000256.3(MYBPC3):​c.2067+118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 1,483,902 control chromosomes in the GnomAD database, including 336,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35900 hom., cov: 32)
  • Exomes 𝑓: 0.67 (300455 hom.)
• Consequence: MYBPC3 NM_000256.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -2.68

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-47339533-T-C is Benign according to our data. Variant chr11-47339533-T-C is described in ClinVar as [Benign]. Clinvar id is 1241464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-47339533-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPC3	NM_000256.3	c.2067+118A>G		intron_variant		ENST00000545968.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC3	ENST00000545968.6	c.2067+118A>G		intron_variant		5	NM_000256.3	P4
MYBPC3	ENST00000399249.6	c.2067+118A>G		intron_variant		5		A2
MYBPC3	ENST00000544791.1	c.2067+118A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103921 AN: 152002 Hom.: 35879 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.668 AC: 889448 AN: 1331784 Hom.: 300455 Cov.: 22 AF XY: 0.669 AC XY: 439372 AN XY: 656362

Gnomad4 AFR exome AF: 0.681

Gnomad4 AMR exome AF: 0.815

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.982

Gnomad4 SAS exome AF: 0.759

Gnomad4 FIN exome AF: 0.699

Gnomad4 NFE exome AF: 0.642

Gnomad4 OTH exome AF: 0.682

GnomAD4 genome AF: 0.684 AC: 103989 AN: 152118 Hom.: 35900 Cov.: 32 AF XY: 0.691 AC XY: 51406 AN XY: 74354

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.672

Alfa AF: 0.652 Hom.: 7402

Bravo AF: 0.688

Asia WGS AF: 0.850 AC: 2954 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.027
DANN	Benign	0.35

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: rs2856653; hg19: chr11-47361084;