dbSNP rs193920840: PLEKHG4B:p.Arg771Trp (chr5-156173-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_052909.5(PLEKHG4B):c.2311C>T(p.Arg771Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,576,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R771Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

PLEKHG4B
NM_052909.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.287

Publications

0 publications found

Variant links:

Genes affected

PLEKHG4B (HGNC:29399): (pleckstrin homology and RhoGEF domain containing G4B) This gene encodes a large protein that contains a pleckstrin homology domain and may function as a guanine nucleotide exchange factor. [provided by RefSeq, May 2017]

PLEKHG4B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09086901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG4B	NM_052909.5 link	c.2311C>T	p.Arg771Trp	missense_variant	Exon 10 of 20	ENST00000637938.2	NP_443141.4	Q96PX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLEKHG4B	ENST00000637938.2 link	c.2311C>T	p.Arg771Trp	missense_variant	Exon 10 of 20	5	NM_052909.5	ENSP00000490806.1	A0A1B0GW72
PLEKHG4B	ENST00000283426.11 link	c.1243C>T	p.Arg415Trp	missense_variant	Exon 8 of 18	1		ENSP00000283426.6	Q96PX9
PLEKHG4B	ENST00000502646.1 link	c.985C>T	p.Arg329Trp	missense_variant	Exon 8 of 9	1		ENSP00000422493.1	Q96HN1

Frequencies

GnomAD3 genomes

AF:

0.0000142

AC:

AN:

140708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000614

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000500

AC:

AN:

240022

AF XY:

0.0000692

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000334

AC:

AN:

1435822

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

714596

show subpopulations

African (AFR)

AF:

0.0000619

AC:

AN:

32288

American (AMR)

AF:

0.00

AC:

AN:

43212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25310

East Asian (EAS)

AF:

0.00

AC:

AN:

38920

South Asian (SAS)

AF:

0.000241

AC:

AN:

82956

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52636

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5630

European-Non Finnish (NFE)

AF:

0.0000219

AC:

AN:

1095982

Other (OTH)

AF:

0.0000340

AC:

AN:

58888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000142

AC:

AN:

140826

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

67528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38174

American (AMR)

AF:

0.00

AC:

AN:

13046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3380

East Asian (EAS)

AF:

0.00

AC:

AN:

4896

South Asian (SAS)

AF:

0.000615

AC:

AN:

3252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65454

Other (OTH)

AF:

0.00

AC:

AN:

1732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000453

Hom.:

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Prostate cancer

Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

.;T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.091

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;M;.

PhyloP100

0.29

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.8

.;D;D

REVEL

Benign

0.16

Sift

Benign

0.18

.;T;T

Sift4G

Benign

0.13

.;T;D

Polyphen

0.88

.;P;.

Vest4

0.29

MutPred

0.47

.;Loss of disorder (P = 1e-04);.;

MVP

0.26

MPC

0.46

ClinPred

0.78

GERP RS

-0.039

Varity_R

0.13

gMVP

0.48

Mutation Taster

=97/3

polymorphism

(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.

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