Variant chr1-227029074-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001394014.1(CDC42BPA):c.4015G>A(p.Val1339Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,613,522 control chromosomes in the GnomAD database, including 80,542 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 6898 hom., cov: 33)

Exomes 𝑓: 0.31 ( 73644 hom. )

Consequence

CDC42BPA
NM_001394014.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.262

Variant links:

Genes affected

CDC42BPA (HGNC:1737): (CDC42 binding protein kinase alpha) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase contains multiple functional domains. Its kinase domain is highly similar to that of the myotonic dystrophy protein kinase (DMPK). This kinase also contains a Rac interactive binding (CRIB) domain, and has been shown to bind CDC42. It may function as a CDC42 downstream effector mediating CDC42 induced peripheral actin formation, and promoting cytoskeletal reorganization. Multiple alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2018]

CDC42BPA 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=0.0029078722).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC42BPA	NM_001394014.1 linkuse as main transcript	c.4015G>A	p.Val1339Ile	missense_variant	30/37	ENST00000366766.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC42BPA	ENST00000366766.8 linkuse as main transcript	c.4015G>A	p.Val1339Ile	missense_variant	30/37	5	NM_001394014.1		Q5VT25-2

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44980

AN:

151996

Hom.:

6893

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.297

GnomAD3 exomes

AF:

0.323

AC:

81094

AN:

250802

Hom.:

13696

AF XY:

0.318

AC XY:

43057

AN XY:

135608

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.397

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.433

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.369

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.308

GnomAD4 exome

AF:

0.314

AC:

458910

AN:

1461408

Hom.:

73644

Cov.:

AF XY:

0.311

AC XY:

225892

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.391

Gnomad4 ASJ exome

AF:

0.294

Gnomad4 EAS exome

AF:

0.419

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.317

Gnomad4 OTH exome

AF:

0.303

GnomAD4 genome

AF:

0.296

AC:

45006

AN:

152114

Hom.:

6898

Cov.:

AF XY:

0.300

AC XY:

22331

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.345

Gnomad4 ASJ

AF:

0.296

Gnomad4 EAS

AF:

0.426

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.382

Gnomad4 NFE

AF:

0.317

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.310

Hom.:

17410

Bravo

AF:

0.294

TwinsUK

AF:

0.333

AC:

1234

ALSPAC

AF:

0.317

AC:

1223

ESP6500AA

AF:

0.218

AC:

962

ESP6500EA

AF:

0.315

AC:

2711

ExAC

AF:

0.317

AC:

38522

Asia WGS

AF:

0.311

AC:

1078

AN:

3478

EpiCase

AF:

0.311

EpiControl

AF:

0.314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.30

DEOGEN2

Benign

0.039

.;T;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.59

T;T;T;T;T

MetaRNN

Benign

0.0029

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.1

.;N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.49

N;.;N;.;.

REVEL

Benign

0.16

Sift

Benign

1.0

T;.;T;.;.

Sift4G

Benign

0.86

T;T;T;T;T

Polyphen

0.0

B;.;B;.;.

Vest4

0.074

MPC

0.19

ClinPred

0.0022

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.026

gMVP

0.099

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

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