rs9321174

Positions:

• chr6-129600071-G-A

Variant summary

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

The NM_033515.3(ARHGAP18):​c.1572+571C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,878 control chromosomes in the GnomAD database, including 7,708 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 0.31 (7708 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.1572+571C>T		intron_variant		ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.1572+571C>T		intron_variant		1	NM_033515.3	ENSP00000357131	P1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47572 AN: 151760 Hom.: 7698 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.314 AC: 47637 AN: 151878 Hom.: 7708 Cov.: 32 AF XY: 0.315 AC XY: 23346 AN XY: 74232

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.319

Alfa AF: 0.345 Hom.: 13511

Bravo AF: 0.311

Asia WGS AF: 0.207 AC: 716 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.89
DANN	Benign	0.26

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: rs9321174; hg19: chr6-129921216;