rs6935162

Variant names:

• chr6-129586442-G-T
• rs6935162
• NM_033515.3:c.1714-2330C>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.1714-2330C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,690 control chromosomes in the GnomAD database, including 5,928 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 0.28 (5928 hom., cov: 31)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.896
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.383 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.1714-2330C>A		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.1714-2330C>A		intron	N/A	ENSP00000357131.2
	ARHGAP18	ENST00000463225.1	TSL:3	n.92-2330C>A		intron	N/A
	ARHGAP18	ENST00000483367.5	TSL:3	n.88-2330C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41727 AN: 151572 Hom.: 5932 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.275 AC: 41717 AN: 151690 Hom.: 5928 Cov.: 31 AF XY: 0.275 AC XY: 20378 AN XY: 74106

African (AFR) AF: 0.206 AC: 8533 AN: 41372

American (AMR) AF: 0.243 AC: 3696 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 970 AN: 3468

East Asian (EAS) AF: 0.255 AC: 1314 AN: 5158

South Asian (SAS) AF: 0.398 AC: 1911 AN: 4798

European-Finnish (FIN) AF: 0.290 AC: 3041 AN: 10488

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21098 AN: 67862

Other (OTH) AF: 0.277 AC: 585 AN: 2112

Alfa AF: 0.302 Hom.: 30352

Bravo AF: 0.267

Asia WGS AF: 0.318 AC: 1111 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.25
PhyloP100		0.90
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: rs6935162; hg19: chr6-129907587; COSMIC: COSV63765939;