rs782780656

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001666.5(ARHGAP4):c.2768G>A(p.Arg923Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,009,152 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 48 hemizygotes in GnomAD. 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 0.000089 ( 0 hom., 2 hem., cov: 25)

Exomes 𝑓: 0.00017 ( 0 hom. 46 hem. )

Consequence

ARHGAP4
NM_001666.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.353

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ARHGAP4 links:

ENSG00000284987 (HGNC:):

ENSG00000284987 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09318632).

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001666.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP4	NM_001666.5	MANE Select	c.2768G>A	p.Arg923Gln	missense	Exon 22 of 22	NP_001657.3
	ARHGAP4	NM_001164741.2		c.2888G>A	p.Arg963Gln	missense	Exon 23 of 23	NP_001158213.1	P98171-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP4	ENST00000350060.10	TSL:1 MANE Select	c.2768G>A	p.Arg923Gln	missense	Exon 22 of 22	ENSP00000203786.8	P98171-1
ARHGAP4	ENST00000370028.7	TSL:1	c.2888G>A	p.Arg963Gln	missense	Exon 23 of 23	ENSP00000359045.3	P98171-2
ENSG00000284987	ENST00000646191.1		n.96+1268G>A		intron	N/A	ENSP00000493873.1	A0A2R8Y4P6

Frequencies

GnomAD3 genomes

AF:

0.0000886

AC:

AN:

112863

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000924

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000119

AC:

AN:

83783

AF XY:

0.0000674

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000209

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000168

AC:

151

AN:

896289

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

AN XY:

280091

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19651

American (AMR)

AF:

0.0000688

AC:

AN:

14530

Ashkenazi Jewish (ASJ)

AF:

0.0000856

AC:

AN:

11678

East Asian (EAS)

AF:

0.00

AC:

AN:

23594

South Asian (SAS)

AF:

0.0000474

AC:

AN:

21119

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31415

Middle Eastern (MID)

AF:

0.000323

AC:

AN:

3097

European-Non Finnish (NFE)

AF:

0.000190

AC:

140

AN:

734974

Other (OTH)

AF:

0.000193

AC:

AN:

36231

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000886

AC:

AN:

112863

Hom.:

Cov.:

AF XY:

0.0000571

AC XY:

AN XY:

35031

show subpopulations

African (AFR)

AF:

0.0000321

AC:

AN:

31128

American (AMR)

AF:

0.0000924

AC:

AN:

10817

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3554

South Asian (SAS)

AF:

0.00

AC:

AN:

2792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6295

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000150

AC:

AN:

53169

Other (OTH)

AF:

0.00

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000102

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.000116

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-1.0

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.14

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.75

M_CAP

Benign

0.014

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.35

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.3

REVEL

Benign

0.012

Sift

Benign

0.042

Sift4G

Benign

0.12

Polyphen

0.0080

Vest4

0.10

MVP

0.27

MPC

0.025

ClinPred

0.078

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.073

gMVP

0.32

Mutation Taster

=100/0

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over