Variant 11-47343463-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000256.3(MYBPC3):c.1223+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,555,348 control chromosomes in the GnomAD database, including 11,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 750 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10723 hom. )

Consequence

MYBPC3
NM_000256.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0660

Variant links:

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]

MYBPC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-47343463-C-T is Benign according to our data. Variant chr11-47343463-C-T is described in ClinVar as [Benign]. Clinvar id is 188543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47343463-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC3	NM_000256.3 link	c.1223+29G>A		intron_variant		ENST00000545968.6	NP_000247.2	Q14896-1A5YM48

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MYBPC3	ENST00000545968.6 link	c.1223+29G>A	intron_variant	5	NM_000256.3	ENSP00000442795.1	Q14896-1
MYBPC3	ENST00000399249.6 link	c.1223+29G>A	intron_variant	5		ENSP00000382193.2	A8MXZ9
MYBPC3	ENST00000544791.1 link	n.1223+29G>A	intron_variant	5		ENSP00000444259.1	F5GZR4

Frequencies

GnomAD3 genomes

AF:

0.0888

AC:

13501

AN:

152026

Hom.:

751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0332

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0743

Gnomad ASJ

AF:

0.0934

Gnomad EAS

AF:

0.0477

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.0843

GnomAD3 exomes

AF:

0.0987

AC:

16530

AN:

167554

Hom.:

991

AF XY:

0.102

AC XY:

9135

AN XY:

89600

show subpopulations

Gnomad AFR exome

AF:

0.0340

Gnomad AMR exome

AF:

0.0468

Gnomad ASJ exome

AF:

0.0897

Gnomad EAS exome

AF:

0.0435

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.120

AC:

168196

AN:

1403206

Hom.:

10723

Cov.:

AF XY:

0.120

AC XY:

82930

AN XY:

692756

show subpopulations

Gnomad4 AFR exome

AF:

0.0305

Gnomad4 AMR exome

AF:

0.0491

Gnomad4 ASJ exome

AF:

0.0927

Gnomad4 EAS exome

AF:

0.0450

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.0887

AC:

13497

AN:

152142

Hom.:

750

Cov.:

AF XY:

0.0875

AC XY:

6507

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0331

Gnomad4 AMR

AF:

0.0741

Gnomad4 ASJ

AF:

0.0934

Gnomad4 EAS

AF:

0.0476

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.0834

Alfa

AF:

0.0707

Hom.:

103

Bravo

AF:

0.0820

Asia WGS

AF:

0.0810

AC:

280

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Left ventricular noncompaction 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Hypertrophic cardiomyopathy 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.4

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over