Variant rs25665 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.1870G>A(p.Val624Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,612,942 control chromosomes in the GnomAD database, including 43,641 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.19 ( 3424 hom., cov: 30)

Exomes 𝑓: 0.23 ( 40217 hom. )

Consequence

MYBPC2
NM_004533.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

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:

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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=0.0034859478).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 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.1870G>A	p.Val624Ile	missense_variant	17/28	ENST00000357701.6	NP_004524.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC2	ENST00000357701.6 linkuse as main transcript	c.1870G>A	p.Val624Ile	missense_variant	17/28	1	NM_004533.4	ENSP00000350332	P1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29143

AN:

151952

Hom.:

3419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0656

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.220

GnomAD3 exomes

AF:

0.258

AC:

63713

AN:

247216

Hom.:

9064

AF XY:

0.258

AC XY:

34651

AN XY:

134250

show subpopulations

Gnomad AFR exome

AF:

0.0595

Gnomad AMR exome

AF:

0.366

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.390

Gnomad SAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.228

AC:

333701

AN:

1460872

Hom.:

40217

Cov.:

AF XY:

0.230

AC XY:

167051

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.0592

Gnomad4 AMR exome

AF:

0.350

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.366

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.192

AC:

29158

AN:

152070

Hom.:

3424

Cov.:

AF XY:

0.199

AC XY:

14764

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0655

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.385

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.222

Alfa

AF:

0.218

Hom.:

8518

Bravo

AF:

0.190

TwinsUK

AF:

0.232

AC:

859

ALSPAC

AF:

0.228

AC:

879

ESP6500AA

AF:

0.0626

AC:

263

ESP6500EA

AF:

0.212

AC:

1778

ExAC

AF:

0.253

AC:

30609

Asia WGS

AF:

0.325

AC:

1132

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0060

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.15

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.87

REVEL

Benign

0.086

Sift

Benign

0.15

Sift4G

Uncertain

0.036

Polyphen

0.041

Vest4

0.040

MPC

0.16

ClinPred

0.0080

GERP RS

-0.48

Varity_R

0.063

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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