11-47340788-G-A

Position:

• chr11-47340788-G-A

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.1927+215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,176 control chromosomes in the GnomAD database, including 6,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (6104 hom., cov: 34)
• Consequence: MYBPC3 NM_000256.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0830

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=-0.88).
• BP6: Variant 11-47340788-G-A is Benign according to our data. Variant chr11-47340788-G-A is described in ClinVar as [Benign]. Clinvar id is 672523.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-47340788-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPC3	NM_000256.3	c.1927+215C>T		intron_variant		ENST00000545968.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC3	ENST00000545968.6	c.1927+215C>T		intron_variant		5	NM_000256.3	P4
MYBPC3	ENST00000399249.6	c.1927+215C>T		intron_variant		5		A2
MYBPC3	ENST00000544791.1	c.1927+215C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39740 AN: 152056 Hom.: 6104 Cov.: 34

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.261 AC: 39750 AN: 152176 Hom.: 6104 Cov.: 34 AF XY: 0.270 AC XY: 20047 AN XY: 74380

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.214

Alfa AF: 0.183 Hom.: 4986

Bravo AF: 0.267

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.21

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: rs10769253; hg19: chr11-47362339;