rs9375644

Variant names:

• chr6-129630856-C-T
• rs9375644
• NM_033515.3:c.617-1334G>A

Variant summary

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

The NM_033515.3(ARHGAP18):​c.617-1334G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,940 control chromosomes in the GnomAD database, including 22,449 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 0.53 (22449 hom., cov: 31)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.617-1334G>A		intron_variant	Intron 4 of 14	ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.617-1334G>A		intron_variant	Intron 4 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80448 AN: 151822 Hom.: 22405 Cov.: 31

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.530 AC: 80556 AN: 151940 Hom.: 22449 Cov.: 31 AF XY: 0.526 AC XY: 39076 AN XY: 74254

African (AFR) AF: 0.706 AC: 29275 AN: 41450

American (AMR) AF: 0.463 AC: 7062 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1469 AN: 3470

East Asian (EAS) AF: 0.339 AC: 1749 AN: 5166

South Asian (SAS) AF: 0.402 AC: 1935 AN: 4810

European-Finnish (FIN) AF: 0.471 AC: 4960 AN: 10530

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.479 AC: 32527 AN: 67948

Other (OTH) AF: 0.538 AC: 1132 AN: 2104

Alfa AF: 0.500 Hom.: 52927

Bravo AF: 0.537

Asia WGS AF: 0.411 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.36
DANN	Benign	0.56
PhyloP100		-1.9
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: rs9375644; hg19: chr6-129952001;