chr11-128969381-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001378024.1(ARHGAP32):​c.5832C>T​(p.Ser1944=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,614,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 0 hom. )

Consequence

ARHGAP32
NM_001378024.1 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.21
Variant links:
Genes affected
ARHGAP32 (HGNC:17399): (Rho GTPase activating protein 32) RICS is a neuron-associated GTPase-activating protein that may regulate dendritic spine morphology and strength by modulating Rho GTPase (see RHOA; MIM 165390) activity (Okabe et al., 2003 [PubMed 12531901]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 11-128969381-G-A is Benign according to our data. Variant chr11-128969381-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041632.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-1.21 with no splicing effect.
BS2
High AC in GnomAd4 at 212 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARHGAP32NM_001378024.1 linkuse as main transcriptc.5832C>T p.Ser1944= synonymous_variant 23/23 ENST00000682385.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARHGAP32ENST00000682385.1 linkuse as main transcriptc.5832C>T p.Ser1944= synonymous_variant 23/23 NM_001378024.1 P3

Frequencies

GnomAD3 genomes
AF:
0.00140
AC:
213
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000772
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00245
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00144
AC:
362
AN:
251472
Hom.:
2
AF XY:
0.00163
AC XY:
221
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00107
Gnomad ASJ exome
AF:
0.000397
Gnomad EAS exome
AF:
0.000815
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.000462
Gnomad NFE exome
AF:
0.00243
Gnomad OTH exome
AF:
0.00130
GnomAD4 exome
AF:
0.00233
AC:
3406
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.00232
AC XY:
1685
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.000448
Gnomad4 AMR exome
AF:
0.00110
Gnomad4 ASJ exome
AF:
0.000268
Gnomad4 EAS exome
AF:
0.000277
Gnomad4 SAS exome
AF:
0.000185
Gnomad4 FIN exome
AF:
0.000468
Gnomad4 NFE exome
AF:
0.00283
Gnomad4 OTH exome
AF:
0.00232
GnomAD4 genome
AF:
0.00139
AC:
212
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.00125
AC XY:
93
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.000505
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.00245
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00229
Hom.:
2
Bravo
AF:
0.00146
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00262
EpiControl
AF:
0.00273

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

ARHGAP32-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesFeb 28, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
2.3
DANN
Benign
0.50

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.

Other links and lift over

dbSNP: rs78689455; hg19: chr11-128839276; COSMIC: COSV100087843; API