Variant rs2856650 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.1091-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,579,618 control chromosomes in the GnomAD database, including 69,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5253 hom., cov: 28)

Exomes 𝑓: 0.30 ( 64496 hom. )

Consequence

MYBPC3
NM_000256.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.102

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=-0.85).

BP6

Variant 11-47343648-G-A is Benign according to our data. Variant chr11-47343648-G-A is described in ClinVar as [Benign]. Clinvar id is 188541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47343648-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC3	NM_000256.3 link	c.1091-24C>T		intron_variant		ENST00000545968.6	NP_000247.2	Q14896-1A5YM48

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MYBPC3	ENST00000545968.6 link	c.1091-24C>T	intron_variant	5	NM_000256.3	ENSP00000442795.1	Q14896-1
MYBPC3	ENST00000399249.6 link	c.1091-24C>T	intron_variant	5		ENSP00000382193.2	A8MXZ9
MYBPC3	ENST00000544791.1 link	n.1091-24C>T	intron_variant	5		ENSP00000444259.1	F5GZR4

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

36879

AN:

150506

Hom.:

5242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0888

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.298

AC:

64539

AN:

216904

Hom.:

10066

AF XY:

0.300

AC XY:

35443

AN XY:

118316

show subpopulations

Gnomad AFR exome

AF:

0.0835

Gnomad AMR exome

AF:

0.369

Gnomad ASJ exome

AF:

0.351

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.247

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.296

AC:

423377

AN:

1428990

Hom.:

64496

Cov.:

AF XY:

0.297

AC XY:

210289

AN XY:

707552

show subpopulations

Gnomad4 AFR exome

AF:

0.0849

Gnomad4 AMR exome

AF:

0.372

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.326

Gnomad4 SAS exome

AF:

0.296

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.299

Gnomad4 OTH exome

AF:

0.299

GnomAD4 genome

AF:

0.245

AC:

36903

AN:

150628

Hom.:

5253

Cov.:

AF XY:

0.245

AC XY:

17995

AN XY:

73450

show subpopulations

Gnomad4 AFR

AF:

0.0887

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.295

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.228

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.270

Hom.:

2947

Bravo

AF:

0.252

Asia WGS

AF:

0.305

AC:

1059

AN:

3472

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, 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	-	- -

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

-0.85

CADD

Benign

2.8

DANN

Benign

0.62

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

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