rs3868142

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001129729.3(PLEKHG4):c.2489G>A(p.Arg830His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,613,356 control chromosomes in the GnomAD database, including 18,351 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 7093 hom., cov: 33)

Exomes 𝑓: 0.092 ( 11258 hom. )

Consequence

PLEKHG4
NM_001129729.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.10

Publications

31 publications found

Variant links:

Genes affected

PLEKHG4 (HGNC:24501): (pleckstrin homology and RhoGEF domain containing G4) The protein encoded by this gene can function as a guanine nucleotide exchange factor (GEF) and may play a role in intracellular signaling and cytoskeleton dynamics at the Golgi apparatus. Polymorphisms in the region of this gene have been found to be associated with spinocerebellar ataxia in some study populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

PLEKHG4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014715791).

BP6

Variant 16-67286320-G-A is Benign according to our data. Variant chr16-67286320-G-A is described in ClinVar as [Benign]. Clinvar id is 129966.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG4	NM_001129729.3 link	c.2489G>A	p.Arg830His	missense_variant	Exon 15 of 22	ENST00000379344.8	NP_001123201.1	Q58EX7-1A0A024R6X4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG4	ENST00000379344.8 link	c.2489G>A	p.Arg830His	missense_variant	Exon 15 of 22	1	NM_001129729.3	ENSP00000368649.3		Q58EX7-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32727

AN:

151952

Hom.:

7059

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.0779

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0605

Gnomad EAS

AF:

0.00482

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0739

Gnomad OTH

AF:

0.163

GnomAD2 exomes

AF:

0.117

AC:

29463

AN:

251458

AF XY:

0.112

show subpopulations

Gnomad AFR exome

AF:

0.570

Gnomad AMR exome

AF:

0.0656

Gnomad ASJ exome

AF:

0.0681

Gnomad EAS exome

AF:

0.00402

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.0783

Gnomad OTH exome

AF:

0.0950

GnomAD4 exome

AF:

0.0917

AC:

134027

AN:

1461286

Hom.:

11258

Cov.:

AF XY:

0.0916

AC XY:

66603

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.583

AC:

19499

AN:

33458

American (AMR)

AF:

0.0689

AC:

3081

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0703

AC:

1836

AN:

26134

East Asian (EAS)

AF:

0.00270

AC:

107

AN:

39696

South Asian (SAS)

AF:

0.143

AC:

12353

AN:

86240

European-Finnish (FIN)

AF:

0.140

AC:

7464

AN:

53408

Middle Eastern (MID)

AF:

0.150

AC:

864

AN:

5768

European-Non Finnish (NFE)

AF:

0.0739

AC:

82112

AN:

1111482

Other (OTH)

AF:

0.111

AC:

6711

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

6746

13492

20237

26983

33729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.216

AC:

32807

AN:

152070

Hom.:

7093

Cov.:

AF XY:

0.214

AC XY:

15919

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.560

AC:

23196

AN:

41434

American (AMR)

AF:

0.109

AC:

1662

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0605

AC:

210

AN:

3472

East Asian (EAS)

AF:

0.00483

AC:

AN:

5176

South Asian (SAS)

AF:

0.138

AC:

666

AN:

4826

European-Finnish (FIN)

AF:

0.148

AC:

1564

AN:

10584

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0739

AC:

5021

AN:

67972

Other (OTH)

AF:

0.161

AC:

340

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

977

1953

2930

3906

4883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.114

Hom.:

10863

Bravo

AF:

0.224

TwinsUK

AF:

0.0777

AC:

288

ALSPAC

AF:

0.0773

AC:

298

ESP6500AA

AF:

0.550

AC:

2418

ESP6500EA

AF:

0.0751

AC:

646

ExAC

AF:

0.129

AC:

15643

Asia WGS

AF:

0.121

AC:

422

AN:

3478

EpiCase

AF:

0.0740

EpiControl

AF:

0.0764

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.91

.;.;D;D

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.6

M;M;M;.

PhyloP100

2.1

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.7

D;D;D;D

REVEL

Benign

0.10

Sift

Uncertain

0.027

D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.038

B;B;B;B

Vest4

0.080

MPC

0.36

ClinPred

0.024

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.095

gMVP

0.18

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs3868142

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