rs12530181

Variant names:

• chr6-129603858-A-G
• rs12530181
• NM_033515.3:c.1365+2019T>C

Variant summary

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

The NM_033515.3(ARHGAP18):​c.1365+2019T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,190 control chromosomes in the GnomAD database, including 2,514 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 (2514 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.1365+2019T>C		intron_variant	Intron 10 of 14	ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.1365+2019T>C		intron_variant	Intron 10 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25732 AN: 152072 Hom.: 2512 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.169 AC: 25765 AN: 152190 Hom.: 2514 Cov.: 32 AF XY: 0.168 AC XY: 12522 AN XY: 74386

African (AFR) AF: 0.103 AC: 4276 AN: 41540

American (AMR) AF: 0.173 AC: 2636 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3472

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5188

South Asian (SAS) AF: 0.147 AC: 709 AN: 4818

European-Finnish (FIN) AF: 0.212 AC: 2246 AN: 10584

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14782 AN: 67990

Other (OTH) AF: 0.170 AC: 360 AN: 2116

Alfa AF: 0.203 Hom.: 5693

Bravo AF: 0.164

Asia WGS AF: 0.0830 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.031
DANN	Benign	0.60
PhyloP100		-1.5
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: rs12530181; hg19: chr6-129925003;