Variant rs2808096 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018287.7(ARHGAP12):c.1325T>C(p.Phe442Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,603,304 control chromosomes in the GnomAD database, including 37,846 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3151 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34695 hom. )

Consequence

ARHGAP12
NM_018287.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05

Variant links:

Genes affected

ARHGAP12 (HGNC:16348): (Rho GTPase activating protein 12) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein may be involved in suppressing tumor formation by regulating cell invasion and adhesion. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ARHGAP12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029663742).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP12	NM_018287.7 linkuse as main transcript	c.1325T>C	p.Phe442Ser	missense_variant	8/20	ENST00000344936.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP12	ENST00000344936.7 linkuse as main transcript	c.1325T>C	p.Phe442Ser	missense_variant	8/20	1	NM_018287.7		Q8IWW6-1

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28548

AN:

151936

Hom.:

3143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0816

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.210

GnomAD3 exomes

AF:

0.221

AC:

55396

AN:

250132

Hom.:

6706

AF XY:

0.223

AC XY:

30213

AN XY:

135250

show subpopulations

Gnomad AFR exome

AF:

0.0797

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.230

Gnomad EAS exome

AF:

0.376

Gnomad SAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.214

AC:

311142

AN:

1451250

Hom.:

34695

Cov.:

AF XY:

0.216

AC XY:

155898

AN XY:

722080

show subpopulations

Gnomad4 AFR exome

AF:

0.0767

Gnomad4 AMR exome

AF:

0.257

Gnomad4 ASJ exome

AF:

0.231

Gnomad4 EAS exome

AF:

0.344

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.220

GnomAD4 genome

AF:

0.188

AC:

28564

AN:

152054

Hom.:

3151

Cov.:

AF XY:

0.191

AC XY:

14212

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0815

Gnomad4 AMR

AF:

0.273

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.275

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.212

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.217

Hom.:

7454

Bravo

AF:

0.190

TwinsUK

AF:

0.207

AC:

767

ALSPAC

AF:

0.210

AC:

810

ESP6500AA

AF:

0.0842

AC:

371

ESP6500EA

AF:

0.212

AC:

1824

ExAC

AF:

0.217

AC:

26400

Asia WGS

AF:

0.318

AC:

1108

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0090

.;.;.;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.61

T;T;T;T

MetaRNN

Benign

0.0030

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.46

.;N;.;N

MutationTaster

Benign

0.85

P;P;P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

0.39

N;N;N;N

REVEL

Benign

0.024

Sift

Benign

0.42

T;T;T;T

Sift4G

Benign

0.41

T;T;T;T

Polyphen

0.0

.;.;B;B

Vest4

0.17

MPC

0.32

ClinPred

0.013

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.16

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over