6-129673510-C-T

Variant names:

• chr6-129673510-C-T
• rs11154490
• NM_033515.3:c.114-31492G>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.114-31492G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,984 control chromosomes in the GnomAD database, including 6,719 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 0.29 (6719 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP18	NM_033515.3	MANE Select	c.114-31492G>A		intron	N/A	NP_277050.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP18	ENST00000368149.3	TSL:1 MANE Select	c.114-31492G>A		intron	N/A	ENSP00000357131.2	Q8N392-1
	ARHGAP18	ENST00000909755.1		c.114-31492G>A		intron	N/A	ENSP00000579814.1
	ARHGAP18	ENST00000938085.1		c.114-31492G>A		intron	N/A	ENSP00000608144.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44685 AN: 151866 Hom.: 6701 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.294 AC: 44750 AN: 151984 Hom.: 6719 Cov.: 32 AF XY: 0.296 AC XY: 21953 AN XY: 74286

African (AFR) AF: 0.254 AC: 10525 AN: 41450

American (AMR) AF: 0.284 AC: 4336 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3468

East Asian (EAS) AF: 0.222 AC: 1152 AN: 5186

South Asian (SAS) AF: 0.255 AC: 1233 AN: 4826

European-Finnish (FIN) AF: 0.341 AC: 3591 AN: 10526

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21758 AN: 67940

Other (OTH) AF: 0.325 AC: 686 AN: 2110

Alfa AF: 0.295 Hom.: 4899

Bravo AF: 0.288

Asia WGS AF: 0.270 AC: 935 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.58
DANN	Benign	0.30
PhyloP100		-1.0
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: rs11154490; hg19: chr6-129994655;