Variant 19-50464383-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004533.4(MYBPC2):c.3266G>A(p.Arg1089His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,609,318 control chromosomes in the GnomAD database, including 30,503 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2310 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28193 hom. )

Consequence

MYBPC2
NM_004533.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.547

Variant links:

Genes affected

MYBPC2 (HGNC:7550): (myosin binding protein C2) This gene encodes a member of the myosin-binding protein C family. This family includes the fast-, slow- and cardiac-type isoforms, each of which is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The protein encoded by this locus is referred to as the fast-type isoform. Mutations in the related but distinct genes encoding the slow-type and cardiac-type isoforms have been associated with distal arthrogryposis, type 1 and hypertrophic cardiomyopathy, respectively. [provided by RefSeq, Jul 2012]

MYBPC2 links:

MYBPC2 (HGNC:):

MYBPC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031134486).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC2	NM_004533.4 linkuse as main transcript	c.3266G>A	p.Arg1089His	missense_variant	27/28	ENST00000357701.6	NP_004524.3	Q14324A0A140VJQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC2	ENST00000357701.6 linkuse as main transcript	c.3266G>A	p.Arg1089His	missense_variant	27/28	1	NM_004533.4	ENSP00000350332.4		Q14324
MYBPC2	ENST00000597498.1 linkuse as main transcript	n.153G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23729

AN:

152036

Hom.:

2310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0412

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.199

AC:

48153

AN:

242206

Hom.:

5344

AF XY:

0.196

AC XY:

25717

AN XY:

131184

show subpopulations

Gnomad AFR exome

AF:

0.0336

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.107

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.205

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.193

AC:

280679

AN:

1457164

Hom.:

28193

Cov.:

AF XY:

0.191

AC XY:

138654

AN XY:

724352

show subpopulations

Gnomad4 AFR exome

AF:

0.0356

Gnomad4 AMR exome

AF:

0.316

Gnomad4 ASJ exome

AF:

0.193

Gnomad4 EAS exome

AF:

0.136

Gnomad4 SAS exome

AF:

0.168

Gnomad4 FIN exome

AF:

0.206

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.156

AC:

23728

AN:

152154

Hom.:

2310

Cov.:

AF XY:

0.159

AC XY:

11827

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0410

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.209

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.186

Hom.:

4213

Bravo

AF:

0.157

TwinsUK

AF:

0.206

AC:

764

ALSPAC

AF:

0.206

AC:

792

ESP6500AA

AF:

0.0406

AC:

171

ESP6500EA

AF:

0.191

AC:

1622

ExAC

AF:

0.193

AC:

23389

Asia WGS

AF:

0.158

AC:

552

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.69

REVEL

Benign

0.056

Sift

Benign

0.56

Sift4G

Benign

0.24

Polyphen

0.0020

Vest4

0.058

MPC

0.18

ClinPred

0.00079

GERP RS

-0.52

Varity_R

0.053

gMVP

0.44

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over