chr6-129649817-C-T

Variant names:

• chr6-129649817-C-T
• rs9398913
• NM_033515.3:c.114-7799G>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.114-7799G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,644 control chromosomes in the GnomAD database, including 16,827 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 0.46 (16827 hom., cov: 31)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 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.114-7799G>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.114-7799G>A		intron	N/A	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69718 AN: 151526 Hom.: 16790 Cov.: 31

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.460 AC: 69815 AN: 151644 Hom.: 16827 Cov.: 31 AF XY: 0.460 AC XY: 34079 AN XY: 74106

African (AFR) AF: 0.616 AC: 25477 AN: 41356

American (AMR) AF: 0.420 AC: 6405 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1344 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2051 AN: 5168

South Asian (SAS) AF: 0.390 AC: 1872 AN: 4802

European-Finnish (FIN) AF: 0.417 AC: 4333 AN: 10392

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26938 AN: 67890

Other (OTH) AF: 0.463 AC: 976 AN: 2108

Alfa AF: 0.417 Hom.: 51351

Bravo AF: 0.467

Asia WGS AF: 0.434 AC: 1507 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.67
DANN	Benign	0.40
PhyloP100		0.029
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: rs9398913; hg19: chr6-129970962; COSMIC: COSV63763829;