Variant chr19-1068739-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012292.5(ARHGAP45):c.416G>A(p.Arg139His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,609,774 control chromosomes in the GnomAD database, including 113,028 homozygotes. 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 Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.41 ( 13117 hom., cov: 32)

Exomes 𝑓: 0.37 ( 99911 hom. )

Consequence

ARHGAP45
NM_012292.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.39

Variant links:

Genes affected

ARHGAP45 (HGNC:17102): (Rho GTPase activating protein 45) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP45 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.250445E-5).

BP6

Variant 19-1068739-G-A is Benign according to our data. Variant chr19-1068739-G-A is described in ClinVar as [Benign]. Clinvar id is 1225485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP45	NM_012292.5 link	c.416G>A	p.Arg139His	missense_variant	Exon 2 of 23	ENST00000313093.7	NP_036424.2	Q92619-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP45	ENST00000313093.7 link	c.416G>A	p.Arg139His	missense_variant	Exon 2 of 23	1	NM_012292.5	ENSP00000316772.2		Q92619-1

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

62149

AN:

151518

Hom.:

13084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.391

GnomAD3 exomes

AF:

0.379

AC:

90238

AN:

238392

Hom.:

17427

AF XY:

0.376

AC XY:

49006

AN XY:

130426

show subpopulations

Gnomad AFR exome

AF:

0.526

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.338

Gnomad SAS exome

AF:

0.383

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.368

AC:

535921

AN:

1458138

Hom.:

99911

Cov.:

AF XY:

0.368

AC XY:

266553

AN XY:

725198

show subpopulations

Gnomad4 AFR exome

AF:

0.516

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.355

Gnomad4 SAS exome

AF:

0.386

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.410

AC:

62228

AN:

151636

Hom.:

13117

Cov.:

AF XY:

0.411

AC XY:

30468

AN XY:

74082

show subpopulations

Gnomad4 AFR

AF:

0.523

Gnomad4 AMR

AF:

0.413

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.365

Gnomad4 FIN

AF:

0.368

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.385

Alfa

AF:

0.370

Hom.:

18548

Bravo

AF:

0.420

TwinsUK

AF:

0.345

AC:

1278

ALSPAC

AF:

0.362

AC:

1396

ESP6500AA

AF:

0.510

AC:

2239

ESP6500EA

AF:

0.351

AC:

3014

ExAC

AF:

0.377

AC:

45282

Asia WGS

AF:

0.351

AC:

1218

AN:

3478

EpiCase

AF:

0.363

EpiControl

AF:

0.356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 30, 2020	This variant is associated with the following publications: (PMID: 9461441, 15593299) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.0040

DANN

Benign

0.92

DEOGEN2

Benign

0.021

.;T;T;.;.

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.33

T;T;T;T;T

MetaRNN

Benign

0.000023

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.75

.;.;N;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.39

N;.;N;.;.

REVEL

Benign

0.10

Sift

Benign

0.27

T;.;T;.;.

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.0030

.;.;B;.;.

Vest4

0.060

MPC

0.89

ClinPred

0.012

GERP RS

-8.4

Varity_R

0.019

gMVP

0.13

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