Variant 10-24584440-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_020824.4(ARHGAP21):c.5849G>C(p.Ser1950Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,610,988 control chromosomes in the GnomAD database, including 215,979 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1950N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.50 ( 19289 hom., cov: 30)

Exomes 𝑓: 0.52 ( 196690 hom. )

Consequence

ARHGAP21
NM_020824.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0630

Variant links:

Genes affected

ARHGAP21 (HGNC:23725): (Rho GTPase activating protein 21) ARHGAP21 functions preferentially as a GTPase-activating protein (GAP) for CDC42 (MIM 116952) and regulates the ARP2/3 complex (MIM 604221) and F-actin dynamics at the Golgi through control of CDC42 activity (Dubois et al., 2005 [PubMed 15793564]).[supplied by OMIM, Mar 2008]

ARHGAP21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant where missense usually causes diseases, ARHGAP21

BP4

Computational evidence support a benign effect (MetaRNN=9.558728E-6).

BP6

Variant 10-24584440-C-G is Benign according to our data. Variant chr10-24584440-C-G is described in ClinVar as [Benign]. Clinvar id is 769365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP21	NM_020824.4 linkuse as main transcript	c.5849G>C	p.Ser1950Thr	missense_variant	26/26	ENST00000396432.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP21	ENST00000396432.7 linkuse as main transcript	c.5849G>C	p.Ser1950Thr	missense_variant	26/26	1	NM_020824.4	A2	Q5T5U3-1

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75888

AN:

151754

Hom.:

19281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.577

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.516

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.528

Gnomad OTH

AF:

0.478

GnomAD3 exomes

AF:

0.528

AC:

131349

AN:

248898

Hom.:

35023

AF XY:

0.528

AC XY:

70946

AN XY:

134488

show subpopulations

Gnomad AFR exome

AF:

0.411

Gnomad AMR exome

AF:

0.565

Gnomad ASJ exome

AF:

0.556

Gnomad EAS exome

AF:

0.579

Gnomad SAS exome

AF:

0.515

Gnomad FIN exome

AF:

0.535

Gnomad NFE exome

AF:

0.525

Gnomad OTH exome

AF:

0.520

GnomAD4 exome

AF:

0.518

AC:

756217

AN:

1459114

Hom.:

196690

Cov.:

AF XY:

0.519

AC XY:

376812

AN XY:

725886

show subpopulations

Gnomad4 AFR exome

AF:

0.407

Gnomad4 AMR exome

AF:

0.560

Gnomad4 ASJ exome

AF:

0.565

Gnomad4 EAS exome

AF:

0.548

Gnomad4 SAS exome

AF:

0.519

Gnomad4 FIN exome

AF:

0.542

Gnomad4 NFE exome

AF:

0.517

Gnomad4 OTH exome

AF:

0.520

GnomAD4 genome

AF:

0.500

AC:

75914

AN:

151874

Hom.:

19289

Cov.:

AF XY:

0.501

AC XY:

37167

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.577

Gnomad4 EAS

AF:

0.581

Gnomad4 SAS

AF:

0.516

Gnomad4 FIN

AF:

0.535

Gnomad4 NFE

AF:

0.528

Gnomad4 OTH

AF:

0.480

Alfa

AF:

0.490

Hom.:

5233

Bravo

AF:

0.494

TwinsUK

AF:

0.524

AC:

1944

ALSPAC

AF:

0.518

AC:

1996

ESP6500AA

AF:

0.417

AC:

1836

ESP6500EA

AF:

0.533

AC:

4582

ExAC

AF:

0.526

AC:

63814

EpiCase

AF:

0.515

EpiControl

AF:

0.509

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 05, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0040

DANN

Benign

0.31

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.0081

T;T;T

MetaRNN

Benign

0.0000096

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

0.40

N;.;.

REVEL

Benign

0.038

Sift

Benign

0.77

T;.;.

Sift4G

Benign

1.0

T;T;T

Vest4

0.094

MPC

0.36

ClinPred

0.018

GERP RS

-11

gMVP

0.18

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