rs9388724

Variant names:

• chr6-129679083-T-C
• rs9388724
• NM_033515.3:c.113+30941A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033515.3(ARHGAP18):​c.113+30941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,204 control chromosomes in the GnomAD database, including 3,226 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 0.19 (3226 hom., cov: 33)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.91
• Publications: 5 publications found

Genes affected

ARHGAP18 (HGNC:21035): (Rho GTPase activating protein 18) Enables GTPase activator activity. Involved in several processes, including regulation of actin filament polymerization; regulation of small GTPase mediated signal transduction; and small GTPase mediated signal transduction. Located in cytosol; nuclear speck; and plasma membrane. Part of cytoplasmic microtubule and ruffle. Implicated in schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.113+30941A>G		intron_variant	Intron 1 of 14	ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.113+30941A>G		intron_variant	Intron 1 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29334 AN: 152084 Hom.: 3223 Cov.: 33

Gnomad AFR AF: 0.0818

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.218

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29349 AN: 152204 Hom.: 3226 Cov.: 33 AF XY: 0.197 AC XY: 14670 AN XY: 74410

African (AFR) AF: 0.0816 AC: 3392 AN: 41560

American (AMR) AF: 0.222 AC: 3399 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1160 AN: 5180

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4820

European-Finnish (FIN) AF: 0.259 AC: 2740 AN: 10580

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16055 AN: 67980

Other (OTH) AF: 0.222 AC: 469 AN: 2116

Alfa AF: 0.226 Hom.: 2321

Bravo AF: 0.183

Asia WGS AF: 0.237 AC: 822 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0010
DANN	Benign	0.43
PhyloP100		-4.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9388724; hg19: chr6-130000228; COSMIC: COSV63763865;