rs7758025

Positions:

• chr6-129597094-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033515.3(ARHGAP18):​c.1713+2122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 151,896 control chromosomes in the GnomAD database, including 2,334 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 0.17 (2334 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP18	NM_033515.3	c.1713+2122G>A		intron_variant		ENST00000368149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.1713+2122G>A		intron_variant		1	NM_033515.3	P1
ARHGAP18	ENST00000463225.1	n.91+1777G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25295 AN: 151786 Hom.: 2333 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.0790

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.167 AC: 25316 AN: 151896 Hom.: 2334 Cov.: 32 AF XY: 0.165 AC XY: 12235 AN XY: 74226

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0724

Gnomad4 SAS AF: 0.0802

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.169

Alfa AF: 0.151 Hom.: 2387

Bravo AF: 0.174

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.34
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs7758025; hg19: chr6-129918239; COSMIC: COSV63766312; COSMIC: COSV63766312;