rs9388721

Positions:

• chr6-129650784-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033515.3(ARHGAP18):​c.114-8766G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,114 control chromosomes in the GnomAD database, including 2,842 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 0.18 (2842 hom., cov: 31)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP18	NM_033515.3	c.114-8766G>A		intron_variant		ENST00000368149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.114-8766G>A		intron_variant		1	NM_033515.3	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27940 AN: 151996 Hom.: 2839 Cov.: 31

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.184 AC: 27954 AN: 152114 Hom.: 2842 Cov.: 31 AF XY: 0.185 AC XY: 13791 AN XY: 74366

Gnomad4 AFR AF: 0.0922

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.208

Alfa AF: 0.216 Hom.: 4947

Bravo AF: 0.176

Asia WGS AF: 0.223 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.9
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs9388721; hg19: chr6-129971929; COSMIC: COSV63763832;