rs11570115

chr11-47333354-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000256.3(MYBPC3):c.3191-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 1,544,986 control chromosomes in the GnomAD database, including 7,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (542 hom., cov: 33)
  • Exomes 𝑓: 0.097 (7373 hom.)
• Consequence: MYBPC3 NM_000256.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.73

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-47333354-T-C is Benign according to our data. Variant chr11-47333354-T-C is described in ClinVar as [Benign]. Clinvar id is 188578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47333354-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPC3	NM_000256.3	c.3191-21A>G		intron_variant		ENST00000545968.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC3	ENST00000545968.6	c.3191-21A>G		intron_variant		5	NM_000256.3	P4
MYBPC3	ENST00000399249.6	c.3191-21A>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10878 AN: 152042 Hom.: 542 Cov.: 33

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0805

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0903

GnomAD3 exomes AF: 0.0705 AC: 11837 AN: 167790 Hom.: 576 AF XY: 0.0708 AC XY: 6340 AN XY: 89546

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.0441

Gnomad ASJ exome AF: 0.0870

Gnomad EAS exome AF: 0.000380

Gnomad SAS exome AF: 0.0296

Gnomad FIN exome AF: 0.0869

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.0737

GnomAD4 exome AF: 0.0970 AC: 135069 AN: 1392826 Hom.: 7373 Cov.: 34 AF XY: 0.0950 AC XY: 65105 AN XY: 685160

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0448

Gnomad4 ASJ exome AF: 0.0832

Gnomad4 EAS exome AF: 0.000162

Gnomad4 SAS exome AF: 0.0302

Gnomad4 FIN exome AF: 0.0907

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.0835

GnomAD4 genome AF: 0.0715 AC: 10873 AN: 152160 Hom.: 542 Cov.: 33 AF XY: 0.0686 AC XY: 5103 AN XY: 74382

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.0580

Gnomad4 ASJ AF: 0.0805

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0309

Gnomad4 FIN AF: 0.0947

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0894

Alfa AF: 0.0944 Hom.: 435

Bravo AF: 0.0668

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	-0.91
Cadd	Benign	0.17
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs11570115; hg19: chr11-47354905; COSMIC: COSV57034284; COSMIC: COSV57034284;