Variant 19-1085864-A-G 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.3269A>G(p.Glu1090Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,609,126 control chromosomes in the GnomAD database, including 200 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 (★★).

Frequency

Genomes: 𝑓 0.020 ( 100 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 100 hom. )

Consequence

ARHGAP45
NM_012292.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.103

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:

ARHGAP45 (HGNC:):

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=0.0020315647).

BP6

Variant 19-1085864-A-G is Benign according to our data. Variant chr19-1085864-A-G is described in ClinVar as [Benign]. Clinvar id is 777348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP45	NM_012292.5 linkuse as main transcript	c.3269A>G	p.Glu1090Gly	missense_variant	23/23	ENST00000313093.7	NP_036424.2	Q92619-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP45	ENST00000313093.7 linkuse as main transcript	c.3269A>G	p.Glu1090Gly	missense_variant	23/23	1	NM_012292.5	ENSP00000316772.2		Q92619-1

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

3063

AN:

150704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0729

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00670

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00531

AC:

1318

AN:

248220

Hom.:

AF XY:

0.00384

AC XY:

518

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.0738

Gnomad AMR exome

AF:

0.00336

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000197

Gnomad OTH exome

AF:

0.00328

GnomAD4 exome

AF:

0.00216

AC:

3151

AN:

1458310

Hom.:

100

Cov.:

AF XY:

0.00189

AC XY:

1368

AN XY:

725672

show subpopulations

Gnomad4 AFR exome

AF:

0.0789

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.0204

AC:

3072

AN:

150816

Hom.:

100

Cov.:

AF XY:

0.0194

AC XY:

1431

AN XY:

73720

show subpopulations

Gnomad4 AFR

AF:

0.0729

Gnomad4 AMR

AF:

0.00669

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.00416

Hom.:

Bravo

AF:

0.0283

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0723

AC:

318

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00636

AC:

771

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.1

DANN

Benign

0.91

DEOGEN2

Benign

0.0062

.;T;.;.;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.54

T;T;T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.14

.;N;.;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

N;N;.;.;N;.

REVEL

Benign

0.023

Sift

Benign

0.18

T;T;.;.;T;.

Sift4G

Benign

0.36

T;T;T;T;T;T

Polyphen

0.0

.;B;.;.;B;.

Vest4

0.022

MVP

0.030

MPC

0.013

ClinPred

0.00069

GERP RS

-1.5

Varity_R

0.054

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

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