rs9483050

Variant names:

• chr6-129640104-A-G
• rs9483050
• NM_033515.3:c.317-1475T>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.317-1475T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 149,660 control chromosomes in the GnomAD database, including 3,762 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 0.22 (3762 hom., cov: 29)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 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.317-1475T>C		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.317-1475T>C		intron	N/A	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 32595 AN: 149566 Hom.: 3752 Cov.: 29

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.218 AC: 32627 AN: 149660 Hom.: 3762 Cov.: 29 AF XY: 0.215 AC XY: 15658 AN XY: 72908

African (AFR) AF: 0.234 AC: 9473 AN: 40548

American (AMR) AF: 0.220 AC: 3278 AN: 14928

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 793 AN: 3462

East Asian (EAS) AF: 0.107 AC: 549 AN: 5152

South Asian (SAS) AF: 0.178 AC: 848 AN: 4764

European-Finnish (FIN) AF: 0.187 AC: 1860 AN: 9934

Middle Eastern (MID) AF: 0.248 AC: 72 AN: 290

European-Non Finnish (NFE) AF: 0.225 AC: 15194 AN: 67584

Other (OTH) AF: 0.220 AC: 459 AN: 2086

Alfa AF: 0.229 Hom.: 6967

Bravo AF: 0.228

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.76
PhyloP100		-0.041
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: rs9483050; hg19: chr6-129961249;