rs12197456

Positions:

• chr6-129584104-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ARHGAP18 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.1722T>C	p.Val574Val	synonymous_variant	13/15	ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.1722T>C	p.Val574Val	synonymous_variant	13/15	1	NM_033515.3	ENSP00000357131.2
ARHGAP18	ENST00000463225.1	n.100T>C		non_coding_transcript_exon_variant	2/4	3
ARHGAP18	ENST00000483367.5	n.96T>C		non_coding_transcript_exon_variant	2/4	3

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

GnomAD3 exomes AF: 0.0524 AC: 13135 AN: 250646 Hom.: 448 AF XY: 0.0531 AC XY: 7188 AN XY: 135454

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 SAS exome AF: 0.0355

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

Gnomad4 AFR exome AF: 0.0149

Gnomad4 AMR exome AF: 0.0291

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.0346

Gnomad4 SAS exome AF: 0.0366

Gnomad4 FIN exome AF: 0.0617

Gnomad4 NFE exome AF: 0.0659

Gnomad4 OTH exome AF: 0.0601

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

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0356

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0651

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0633 Hom.: 579

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs12197456; hg19: chr6-129905249;