11-47343463-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 4
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
left ventricular noncompaction 10
Inheritance: AR, AD Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
atrial fibrillation
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

MYBPC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 188543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3 link	c.1223+29G>A		intron_variant	Intron 13 of 34	ENST00000545968.6	NP_000247.2	Q14896-1A5YM48

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYBPC3	ENST00000545968.6 link	c.1223+29G>A	intron_variant	Intron 13 of 34	5	NM_000256.3	ENSP00000442795.1	Q14896-1
MYBPC3	ENST00000399249.6 link	c.1223+29G>A	intron_variant	Intron 12 of 33	5		ENSP00000382193.2	A8MXZ9
MYBPC3	ENST00000544791.1 link	n.1223+29G>A	intron_variant	Intron 13 of 26	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

GnomAD2 exomes

AF:

0.0987

AC:

16530

AN:

167554

AF XY:

0.102

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 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

African (AFR)

AF:

0.0305

AC:

978

AN:

32076

American (AMR)

AF:

0.0491

AC:

1814

AN:

36964

Ashkenazi Jewish (ASJ)

AF:

0.0927

AC:

2314

AN:

24962

East Asian (EAS)

AF:

0.0450

AC:

1646

AN:

36586

South Asian (SAS)

AF:

0.116

AC:

9217

AN:

79616

European-Finnish (FIN)

AF:

0.126

AC:

5981

AN:

47372

Middle Eastern (MID)

AF:

0.106

AC:

530

AN:

5022

European-Non Finnish (NFE)

AF:

0.129

AC:

139268

AN:

1082434

Other (OTH)

AF:

0.111

AC:

6448

AN:

58174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.567

Heterozygous variant carriers

7969

15938

23906

31875

39844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5106

10212

15318

20424

25530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0887

AC:

13497

AN:

152142

Hom.:

750

Cov.:

AF XY:

0.0875

AC XY:

6507

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0331

AC:

1373

AN:

41516

American (AMR)

AF:

0.0741

AC:

1134

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0934

AC:

324

AN:

3470

East Asian (EAS)

AF:

0.0476

AC:

246

AN:

5168

South Asian (SAS)

AF:

0.114

AC:

549

AN:

4816

European-Finnish (FIN)

AF:

0.118

AC:

1254

AN:

10602

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8370

AN:

67956

Other (OTH)

AF:

0.0834

AC:

176

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

628

1257

1885

2514

3142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0696

Hom.:

105

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

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

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Left ventricular noncompaction 10

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy 4

Benign:1

Sep 05, 2021

Genome-Nilou Lab

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

-0.87

CADD

Benign

3.4

(source)

DANN

Benign

0.56

PhyloP100

0.066

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over