Variant X-153909144-C-T 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_001666.5(ARHGAP4):c.2533G>A(p.Ala845Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,376 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

ARHGAP4
NM_001666.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.882

Variant links:

Genes affected

ARHGAP4 (HGNC:674): (Rho GTPase activating protein 4) This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins belonging to the RAS superfamily. The protein encoded by the orthologous gene in rat is localized to the Golgi complex and can redistribute to microtubules. The rat protein stimulates the activity of some Rho GTPases in vitro. Genomic deletions of this gene and a neighboring gene have been found in patients with nephrogenic diabetes insipidus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ARHGAP4 links:

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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=0.05286762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP4	NM_001666.5 linkuse as main transcript	c.2533G>A	p.Ala845Thr	missense_variant	21/22	ENST00000350060.10	NP_001657.3
ARHGAP4	NM_001164741.2 linkuse as main transcript	c.2653G>A	p.Ala885Thr	missense_variant	22/23		NP_001158213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP4	ENST00000350060.10 linkuse as main transcript	c.2533G>A	p.Ala845Thr	missense_variant	21/22	1	NM_001666.5	ENSP00000203786	P2	P98171-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1096376

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

361958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

ARHGAP4: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.4

DANN

Benign

0.70

DEOGEN2

Benign

0.042

.;.;T;T

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.053

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

.;.;N;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.10

N;N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.23

T;T;T;T

Sift4G

Benign

0.51

T;T;T;T

Polyphen

0.0010

.;.;B;.

Vest4

0.057

MutPred

0.14

.;.;Gain of glycosylation at A845 (P = 0.0059);.;

MVP

0.093

MPC

0.023

ClinPred

0.029

GERP RS

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.046

gMVP

0.35

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over