chr11-47332517-G-A

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.3627+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,578,520 control chromosomes in the GnomAD database, including 41,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6373 hom., cov: 33)

Exomes 𝑓: 0.20 ( 35268 hom. )

Consequence

MYBPC3
NM_000256.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.26

Publications

17 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=-0.93).

BP6

Variant 11-47332517-G-A is Benign according to our data. Variant chr11-47332517-G-A is described in ClinVar as Benign. ClinVar VariationId is 255625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3 link	c.3627+49C>T		intron_variant	Intron 32 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.3627+49C>T		intron_variant	Intron 32 of 34	5	NM_000256.3	ENSP00000442795.1		Q14896-1
MYBPC3	ENST00000399249.6 link	c.3627+49C>T		intron_variant	Intron 31 of 33	5		ENSP00000382193.2		A8MXZ9

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40262

AN:

151996

Hom.:

6372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.219

GnomAD2 exomes

AF:

0.262

AC:

59661

AN:

227806

AF XY:

0.249

show subpopulations

Gnomad AFR exome

AF:

0.382

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.613

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.203

AC:

289685

AN:

1426406

Hom.:

35268

Cov.:

AF XY:

0.202

AC XY:

142512

AN XY:

705118

show subpopulations

African (AFR)

AF:

0.379

AC:

12355

AN:

32582

American (AMR)

AF:

0.369

AC:

15230

AN:

41296

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

4218

AN:

24080

East Asian (EAS)

AF:

0.604

AC:

23679

AN:

39182

South Asian (SAS)

AF:

0.235

AC:

19322

AN:

82328

European-Finnish (FIN)

AF:

0.268

AC:

13717

AN:

51088

Middle Eastern (MID)

AF:

0.163

AC:

912

AN:

5592

European-Non Finnish (NFE)

AF:

0.172

AC:

187894

AN:

1091640

Other (OTH)

AF:

0.211

AC:

12358

AN:

58618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

12286

24572

36859

49145

61431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7284

14568

21852

29136

36420

<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:

0.265

AC:

40273

AN:

152114

Hom.:

6373

Cov.:

AF XY:

0.273

AC XY:

20292

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.380

AC:

15772

AN:

41474

American (AMR)

AF:

0.271

AC:

4152

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

606

AN:

3472

East Asian (EAS)

AF:

0.595

AC:

3069

AN:

5160

South Asian (SAS)

AF:

0.236

AC:

1138

AN:

4816

European-Finnish (FIN)

AF:

0.298

AC:

3155

AN:

10588

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.173

AC:

11772

AN:

67990

Other (OTH)

AF:

0.216

AC:

456

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1433

2867

4300

5734

7167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.246

Hom.:

1528

Bravo

AF:

0.271

Asia WGS

AF:

0.326

AC:

1132

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.93

CADD

Benign

0.091

(source)

DANN

Benign

0.59

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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