rs3729948

Variant summary

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

The NM_000256.3(MYBPC3):​c.2308+18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 1,613,746 control chromosomes in the GnomAD database, including 1,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 265 hom., cov: 32)
Exomes 𝑓: 0.042 ( 1695 hom. )

Consequence

MYBPC3
NM_000256.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.644
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 11-47338502-G-C is Benign according to our data. Variant chr11-47338502-G-C is described in ClinVar as [Benign]. Clinvar id is 188566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47338502-G-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYBPC3NM_000256.3 linkuse as main transcriptc.2308+18C>G intron_variant ENST00000545968.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYBPC3ENST00000545968.6 linkuse as main transcriptc.2308+18C>G intron_variant 5 NM_000256.3 P4Q14896-1
MYBPC3ENST00000399249.6 linkuse as main transcriptc.2308+18C>G intron_variant 5 A2
MYBPC3ENST00000544791.1 linkuse as main transcriptc.2308+18C>G intron_variant, NMD_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0508
AC:
7736
AN:
152156
Hom.:
266
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0803
Gnomad AMI
AF:
0.0230
Gnomad AMR
AF:
0.0228
Gnomad ASJ
AF:
0.0156
Gnomad EAS
AF:
0.0433
Gnomad SAS
AF:
0.119
Gnomad FIN
AF:
0.0465
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0382
Gnomad OTH
AF:
0.0445
GnomAD3 exomes
AF:
0.0483
AC:
12007
AN:
248776
Hom.:
458
AF XY:
0.0515
AC XY:
6957
AN XY:
134972
show subpopulations
Gnomad AFR exome
AF:
0.0826
Gnomad AMR exome
AF:
0.0156
Gnomad ASJ exome
AF:
0.0125
Gnomad EAS exome
AF:
0.0381
Gnomad SAS exome
AF:
0.120
Gnomad FIN exome
AF:
0.0499
Gnomad NFE exome
AF:
0.0392
Gnomad OTH exome
AF:
0.0361
GnomAD4 exome
AF:
0.0419
AC:
61298
AN:
1461472
Hom.:
1695
Cov.:
31
AF XY:
0.0441
AC XY:
32047
AN XY:
727024
show subpopulations
Gnomad4 AFR exome
AF:
0.0843
Gnomad4 AMR exome
AF:
0.0170
Gnomad4 ASJ exome
AF:
0.0126
Gnomad4 EAS exome
AF:
0.0353
Gnomad4 SAS exome
AF:
0.112
Gnomad4 FIN exome
AF:
0.0501
Gnomad4 NFE exome
AF:
0.0366
Gnomad4 OTH exome
AF:
0.0455
GnomAD4 genome
AF:
0.0508
AC:
7739
AN:
152274
Hom.:
265
Cov.:
32
AF XY:
0.0513
AC XY:
3816
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0804
Gnomad4 AMR
AF:
0.0227
Gnomad4 ASJ
AF:
0.0156
Gnomad4 EAS
AF:
0.0426
Gnomad4 SAS
AF:
0.118
Gnomad4 FIN
AF:
0.0465
Gnomad4 NFE
AF:
0.0381
Gnomad4 OTH
AF:
0.0445
Alfa
AF:
0.0435
Hom.:
34
Bravo
AF:
0.0481
Asia WGS
AF:
0.119
AC:
413
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Hypertrophic cardiomyopathy 4 Benign:3
Benign, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, University Medical Center UtrechtJul 28, 2017- -
Benign, criteria provided, single submitterclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical CenterSep 21, 2015- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Hypertrophic cardiomyopathy Benign:2
Benign, no assertion criteria providedclinical testingCohesion PhenomicsOct 10, 2022- -
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
9.0
DANN
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs3729948; hg19: chr11-47360053; COSMIC: COSV57027816; API