rs11154491

Positions:

• chr6-129690521-A-G

Variant summary

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

The NM_033515.3(ARHGAP18):​c.113+19503T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,168 control chromosomes in the GnomAD database, including 2,891 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 0.17 (2891 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.874

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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.113+19503T>C		intron_variant		ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.113+19503T>C		intron_variant		1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25410 AN: 152050 Hom.: 2881 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.167 AC: 25460 AN: 152168 Hom.: 2891 Cov.: 32 AF XY: 0.169 AC XY: 12536 AN XY: 74390

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0885

Gnomad4 OTH AF: 0.164

Alfa AF: 0.123 Hom.: 751

Bravo AF: 0.184

Asia WGS AF: 0.166 AC: 573 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11154491; hg19: chr6-130011666;