rs12197456

Variant names:

• chr6-129584104-A-G
• rs12197456
• NM_033515.3:c.1722T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033515.3(ARHGAP18):​c.1722T>C​(p.Val574Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.0599 in 1,613,446 control chromosomes in the GnomAD database, including 3,219 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 0.048 (226 hom., cov: 32)
  • Exomes 𝑓: 0.061 (2993 hom.)
• Consequence: ARHGAP18 NM_033515.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17
• Publications: 10 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=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0635 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.1722T>C	p.Val574Val	synonymous	Exon 13 of 15	NP_277050.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP18	ENST00000368149.3	TSL:1 MANE Select	c.1722T>C	p.Val574Val	synonymous	Exon 13 of 15	ENSP00000357131.2
	ARHGAP18	ENST00000463225.1	TSL:3	n.100T>C		non_coding_transcript_exon	Exon 2 of 4
	ARHGAP18	ENST00000483367.5	TSL:3	n.96T>C		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7239 AN: 152116 Hom.: 226 Cov.: 32

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0357

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.0255

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0651

Gnomad OTH AF: 0.0541

GnomAD2 exomes AF: 0.0524 AC: 13135 AN: 250646 AF XY: 0.0531

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.0276

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.0235

Gnomad FIN exome AF: 0.0649

Gnomad NFE exome AF: 0.0670

Gnomad OTH exome AF: 0.0642

GnomAD4 exome AF: 0.0612 AC: 89493 AN: 1461212 Hom.: 2993 Cov.: 32 AF XY: 0.0608 AC XY: 44208 AN XY: 726884

African (AFR) AF: 0.0149 AC: 500 AN: 33452

American (AMR) AF: 0.0291 AC: 1300 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2669 AN: 26116

East Asian (EAS) AF: 0.0346 AC: 1372 AN: 39626

South Asian (SAS) AF: 0.0366 AC: 3158 AN: 86242

European-Finnish (FIN) AF: 0.0617 AC: 3293 AN: 53368

Middle Eastern (MID) AF: 0.0504 AC: 290 AN: 5754

European-Non Finnish (NFE) AF: 0.0659 AC: 73280 AN: 1111610

Other (OTH) AF: 0.0601 AC: 3631 AN: 60366

GnomAD4 genome AF: 0.0475 AC: 7233 AN: 152234 Hom.: 226 Cov.: 32 AF XY: 0.0466 AC XY: 3467 AN XY: 74424

African (AFR) AF: 0.0168 AC: 700 AN: 41550

American (AMR) AF: 0.0356 AC: 544 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3470

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5170

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4820

European-Finnish (FIN) AF: 0.0664 AC: 704 AN: 10600

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0651 AC: 4429 AN: 68018

Other (OTH) AF: 0.0535 AC: 113 AN: 2112

Alfa AF: 0.0616 Hom.: 801

Bravo AF: 0.0451

Asia WGS AF: 0.0370 AC: 129 AN: 3478

EpiCase AF: 0.0624

EpiControl AF: 0.0638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12197456; hg19: chr6-129905249;