Variant 11-73660759-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021200.3(PLEKHB1):c.502G>A(p.Val168Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,592,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

PLEKHB1
NM_021200.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.935

Variant links:

Genes affected

PLEKHB1 (HGNC:19079): (pleckstrin homology domain containing B1) Predicted to enable protein C-terminus binding activity and protein homodimerization activity. Predicted to be involved in regulation of cell differentiation. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHB1 links:

PLEKHB1 (HGNC:):

PLEKHB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030771047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHB1	NM_021200.3 linkuse as main transcript	c.502G>A	p.Val168Ile	missense_variant	7/8	ENST00000354190.10	NP_067023.1	Q9UF11-1A0A024R5H9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHB1	ENST00000354190.10 linkuse as main transcript	c.502G>A	p.Val168Ile	missense_variant	7/8	1	NM_021200.3	ENSP00000346127.5		Q9UF11-1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000241

AC:

AN:

215340

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

116260

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000384

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000532

Gnomad NFE exome

AF:

0.000391

Gnomad OTH exome

AF:

0.000186

GnomAD4 exome

AF:

0.000262

AC:

377

AN:

1440180

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

178

AN XY:

714346

show subpopulations

Gnomad4 AFR exome

AF:

0.0000609

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.0000391

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000389

Gnomad4 NFE exome

AF:

0.000304

Gnomad4 OTH exome

AF:

0.000369

GnomAD4 genome

AF:

0.000236

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000234

Hom.:

Bravo

AF:

0.000283

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000604

AC:

ExAC

AF:

0.000160

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.502G>A (p.V168I) alteration is located in exon 7 (coding exon 7) of the PLEKHB1 gene. This alteration results from a G to A substitution at nucleotide position 502, causing the valine (V) at amino acid position 168 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;.;.;.;.;.;T;T;T;.;T;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.76

T;T;.;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.031

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.46

N;.;.;.;.;.;.;.;.;.;.;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.52

N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.45

T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.97

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.014

B;B;.;.;.;.;.;.;.;.;.;.

Vest4

0.23

MVP

0.16

MPC

0.14

ClinPred

0.019

GERP RS

-0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.049

gMVP

0.51

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over