rs146176251

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000361627.8(ARHGAP11A):ā€‹c.1355C>Gā€‹(p.Ser452Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000719 in 1,597,054 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: š‘“ 0.0038 ( 3 hom., cov: 33)
Exomes š‘“: 0.00040 ( 2 hom. )

Consequence

ARHGAP11A
ENST00000361627.8 missense

Scores

8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28
Variant links:
Genes affected
ARHGAP11A (HGNC:15783): (Rho GTPase activating protein 11A) This gene encodes a member of the Rho GTPase activating protein family. In response to DNA damage, the encoded protein interacts with the p53 tumor suppressor protein and stimulates its tetramerization, which results in cell-cycle arrest and apoptosis. A chromosomal deletion that includes this gene is one cause of Prader-Willi syndrome, and an intronic variant of this gene may be associated with sleep duration in children. This gene is highly expressed in colon cancers and in a human basal-like breast cancer cell line. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0053740144).
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARHGAP11ANM_014783.6 linkuse as main transcriptc.1355C>G p.Ser452Cys missense_variant 11/12 ENST00000361627.8 NP_055598.1
ARHGAP11A-SCG5NM_001368319.1 linkuse as main transcriptc.1235+2679C>G intron_variant NP_001355248.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARHGAP11AENST00000361627.8 linkuse as main transcriptc.1355C>G p.Ser452Cys missense_variant 11/121 NM_014783.6 ENSP00000355090 P1Q6P4F7-1
ENST00000647892.1 linkuse as main transcriptn.574+1232G>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00376
AC:
570
AN:
151548
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0130
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000625
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00100
AC:
240
AN:
239390
Hom.:
1
AF XY:
0.000555
AC XY:
72
AN XY:
129764
show subpopulations
Gnomad AFR exome
AF:
0.0135
Gnomad AMR exome
AF:
0.000796
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000273
Gnomad OTH exome
AF:
0.000345
GnomAD4 exome
AF:
0.000400
AC:
578
AN:
1445396
Hom.:
2
Cov.:
31
AF XY:
0.000337
AC XY:
242
AN XY:
718902
show subpopulations
Gnomad4 AFR exome
AF:
0.0130
Gnomad4 AMR exome
AF:
0.000841
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000964
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000262
Gnomad4 OTH exome
AF:
0.00124
GnomAD4 genome
AF:
0.00376
AC:
570
AN:
151658
Hom.:
3
Cov.:
33
AF XY:
0.00358
AC XY:
265
AN XY:
74062
show subpopulations
Gnomad4 AFR
AF:
0.0129
Gnomad4 AMR
AF:
0.00151
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000626
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00120
Hom.:
0
Bravo
AF:
0.00451
ESP6500AA
AF:
0.0145
AC:
64
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00122
AC:
148
Asia WGS
AF:
0.000289
AC:
1
AN:
3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
.;T;.;.;.
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.70
.;T;T;.;T
MetaRNN
Benign
0.0054
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
.;M;M;.;.
MutationTaster
Benign
0.88
D;D;D;D;D
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-3.0
D;D;D;D;D
REVEL
Benign
0.13
Sift
Uncertain
0.0090
D;D;D;D;D
Sift4G
Uncertain
0.023
D;D;D;D;D
Polyphen
1.0
.;D;.;.;.
Vest4
0.25
MVP
0.65
MPC
0.040
ClinPred
0.044
T
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.18
gMVP
0.16

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: rs146176251; hg19: chr15-32927988; API