rs4504494

Variant names:

• chr6-129591942-G-A
• rs4504494
• NM_033515.3:c.1713+7274C>T

Variant summary

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

The NM_033515.3(ARHGAP18):​c.1713+7274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,012 control chromosomes in the GnomAD database, including 5,899 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 0.20 (5899 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.1713+7274C>T		intron_variant	Intron 12 of 14	ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.1713+7274C>T		intron_variant	Intron 12 of 14	1	NM_033515.3	ENSP00000357131.2
ARHGAP18	ENST00000463225.1	n.91+6929C>T		intron_variant	Intron 1 of 3	3
ARHGAP18	ENST00000483367.5	n.87+4847C>T		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30523 AN: 151894 Hom.: 5877 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.201 AC: 30613 AN: 152012 Hom.: 5899 Cov.: 32 AF XY: 0.203 AC XY: 15062 AN XY: 74314

African (AFR) AF: 0.478 AC: 19801 AN: 41400

American (AMR) AF: 0.286 AC: 4368 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3472

East Asian (EAS) AF: 0.311 AC: 1607 AN: 5162

South Asian (SAS) AF: 0.148 AC: 711 AN: 4820

European-Finnish (FIN) AF: 0.0280 AC: 296 AN: 10578

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0452 AC: 3076 AN: 67988

Other (OTH) AF: 0.184 AC: 388 AN: 2112

Alfa AF: 0.0953 Hom.: 7476

Bravo AF: 0.233

Asia WGS AF: 0.239 AC: 830 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.53
PhyloP100		0.034
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: rs4504494; hg19: chr6-129913087; COSMIC: COSV63763450;