rs1023480

Variant names:

• chr6-129703055-G-A
• rs1023480
• NM_033515.3:c.113+6969C>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.113+6969C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,944 control chromosomes in the GnomAD database, including 17,199 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 0.45 (17199 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.113+6969C>T		intron_variant	Intron 1 of 14	ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.113+6969C>T		intron_variant	Intron 1 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68446 AN: 151826 Hom.: 17194 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.450 AC: 68450 AN: 151944 Hom.: 17199 Cov.: 32 AF XY: 0.447 AC XY: 33180 AN XY: 74238

African (AFR) AF: 0.238 AC: 9859 AN: 41460

American (AMR) AF: 0.431 AC: 6594 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1947 AN: 3468

East Asian (EAS) AF: 0.212 AC: 1096 AN: 5164

South Asian (SAS) AF: 0.536 AC: 2584 AN: 4824

European-Finnish (FIN) AF: 0.530 AC: 5556 AN: 10488

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39085 AN: 67950

Other (OTH) AF: 0.445 AC: 937 AN: 2104

Alfa AF: 0.538 Hom.: 38003

Bravo AF: 0.432

Asia WGS AF: 0.376 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.65
DANN	Benign	0.52
PhyloP100		-0.88
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: rs1023480; hg19: chr6-130024200;