Variant rs3729802 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.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

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:

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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=-0.93).

BP6

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

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/exons	MANE	Protein	UniProt
MYBPC3	NM_000256.3 link	c.3627+49C>T		intron_variant		ENST00000545968.6	NP_000247.2	Q14896-1A5YM48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6 link	c.3627+49C>T		intron_variant		5	NM_000256.3	ENSP00000442795.1		Q14896-1
MYBPC3	ENST00000399249.6 link	c.3627+49C>T		intron_variant		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

GnomAD3 exomes

AF:

0.262

AC:

59661

AN:

227806

Hom.:

10071

AF XY:

0.249

AC XY:

30718

AN XY:

123396

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 SAS exome

AF:

0.225

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

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.369

Gnomad4 ASJ exome

AF:

0.175

Gnomad4 EAS exome

AF:

0.604

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.268

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.265

AC:

40273

AN:

152114

Hom.:

6373

Cov.:

AF XY:

0.273

AC XY:

20292

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.380

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.595

Gnomad4 SAS

AF:

0.236

Gnomad4 FIN

AF:

0.298

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.205

Hom.:

689

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.091

DANN

Benign

0.59

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