rs16992796

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181335.3(ARHGAP8):​c.79+528A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 151,992 control chromosomes in the GnomAD database, including 1,429 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1429 hom., cov: 33)

Consequence

ARHGAP8
NM_181335.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58
Variant links:
Genes affected
ARHGAP8 (HGNC:677): (Rho GTPase activating protein 8) This gene encodes a member of the RHOGAP family. GAP (GTPase-activating) family proteins participate in signaling pathways that regulate cell processes involved in cytoskeletal changes. GAP proteins alternate between an active (GTP-bound) and inactive (GDP-bound) state based on the GTP:GDP ratio in the cell. This family member is a multidomain protein that functions to promote Erk activation and cell motility. Alternative splicing results in multiple transcript variants. Read-through transcripts from the upstream proline rich 5, renal (PRR5) gene into this gene also exist, which led to the original description of PRR5 and ARHGAP8 being a single gene. [provided by RefSeq, Nov 2010]
PRR5-ARHGAP8 (HGNC:34512): (PRR5-ARHGAP8 readthrough) The PRR5-ARHGAP8 mRNA is an infrequent but naturally occurring read-through transcript of the neighboring proline rich 5, renal (PRR5) and Rho GTPase activating protein 8 (ARHGAP8) genes. The resulting fusion protein contains sequence identity with each individual gene product, and it includes domains characteristic of a RhoGAP protein. The significance of this read-through transcript and the function of its protein product have not yet been determined. [provided by RefSeq, Nov 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGAP8NM_181335.3 linkc.79+528A>G intron_variant Intron 2 of 11 ENST00000356099.11 NP_851852.2 P85298-4Q6PJW1
PRR5-ARHGAP8NM_181334.6 linkc.472+528A>G intron_variant Intron 5 of 14 NP_851851.3 B1AHC3
ARHGAP8NM_001017526.2 linkc.79+528A>G intron_variant Intron 2 of 12 NP_001017526.1 P85298-1Q6PJW1
ARHGAP8NM_001198726.2 linkc.79+528A>G intron_variant Intron 2 of 10 NP_001185655.1 P85298-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGAP8ENST00000356099.11 linkc.79+528A>G intron_variant Intron 2 of 11 1 NM_181335.3 ENSP00000348407.6 P85298-4
PRR5-ARHGAP8ENST00000352766.11 linkc.841+528A>G intron_variant Intron 8 of 16 2 ENSP00000262731.11 B1AHC4

Frequencies

GnomAD3 genomes
AF:
0.115
AC:
17532
AN:
151876
Hom.:
1428
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.238
Gnomad AMI
AF:
0.0504
Gnomad AMR
AF:
0.0859
Gnomad ASJ
AF:
0.103
Gnomad EAS
AF:
0.0871
Gnomad SAS
AF:
0.0916
Gnomad FIN
AF:
0.0672
Gnomad MID
AF:
0.0823
Gnomad NFE
AF:
0.0610
Gnomad OTH
AF:
0.107
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.115
AC:
17549
AN:
151992
Hom.:
1429
Cov.:
33
AF XY:
0.114
AC XY:
8457
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.238
Gnomad4 AMR
AF:
0.0858
Gnomad4 ASJ
AF:
0.103
Gnomad4 EAS
AF:
0.0870
Gnomad4 SAS
AF:
0.0909
Gnomad4 FIN
AF:
0.0672
Gnomad4 NFE
AF:
0.0611
Gnomad4 OTH
AF:
0.108
Alfa
AF:
0.0725
Hom.:
808
Bravo
AF:
0.120
Asia WGS
AF:
0.110
AC:
385
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.30
DANN
Benign
0.52

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: rs16992796; hg19: chr22-45183014; API