rs10499163

Variant names:

• chr6-129641488-T-C
• rs10499163
• NM_033515.3:c.316+328A>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.316+328A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,034 control chromosomes in the GnomAD database, including 6,341 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 0.28 (6341 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033515.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP18	NM_033515.3	MANE Select	c.316+328A>G		intron	N/A	NP_277050.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP18	ENST00000368149.3	TSL:1 MANE Select	c.316+328A>G		intron	N/A	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43269 AN: 151916 Hom.: 6333 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.285 AC: 43303 AN: 152034 Hom.: 6341 Cov.: 32 AF XY: 0.284 AC XY: 21098 AN XY: 74348

African (AFR) AF: 0.266 AC: 11029 AN: 41450

American (AMR) AF: 0.258 AC: 3942 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3468

East Asian (EAS) AF: 0.250 AC: 1289 AN: 5166

South Asian (SAS) AF: 0.265 AC: 1279 AN: 4824

European-Finnish (FIN) AF: 0.329 AC: 3483 AN: 10582

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20517 AN: 67938

Other (OTH) AF: 0.303 AC: 641 AN: 2114

Alfa AF: 0.292 Hom.: 21463

Bravo AF: 0.275

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.8
DANN	Benign	0.82
PhyloP100		-1.4
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: rs10499163; hg19: chr6-129962633;