rs11570115

Variant names:

Variant summary

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

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 (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.071 ( 542 hom., cov: 33)

Exomes 𝑓: 0.097 ( 7373 hom. )

Consequence

MYBPC3
NM_000256.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.73

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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3 link	c.3191-21A>G		intron_variant	Intron 29 of 34	ENST00000545968.6	NP_000247.2	Q14896-1A5YM48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6 link	c.3191-21A>G		intron_variant	Intron 29 of 34	5	NM_000256.3	ENSP00000442795.1		Q14896-1
MYBPC3	ENST00000399249.6 link	c.3191-21A>G		intron_variant	Intron 28 of 33	5		ENSP00000382193.2		A8MXZ9

Frequencies

GnomAD3 genomes

AF:

0.0715

AC:

10878

AN:

152042

Hom.:

542

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0950

AC XY:

65105

AN XY:

685160

show subpopulations

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.:

AF XY:

0.0686

AC XY:

5103

AN XY:

74382

show subpopulations

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:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.17

DANN

Benign

0.30

BranchPoint Hunter

1.0

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

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