NM_033515.3:c.553-237G>A

Variant names:

• chr6-129634342-C-T
• rs4509146
• NM_033515.3:c.553-237G>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.553-237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,848 control chromosomes in the GnomAD database, including 5,799 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 0.27 (5799 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.553-237G>A		intron_variant	Intron 3 of 14	ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.553-237G>A		intron_variant	Intron 3 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40222 AN: 151730 Hom.: 5792 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.265 AC: 40250 AN: 151848 Hom.: 5799 Cov.: 32 AF XY: 0.264 AC XY: 19597 AN XY: 74198

African (AFR) AF: 0.155 AC: 6431 AN: 41424

American (AMR) AF: 0.279 AC: 4254 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1019 AN: 3470

East Asian (EAS) AF: 0.170 AC: 877 AN: 5168

South Asian (SAS) AF: 0.236 AC: 1136 AN: 4806

European-Finnish (FIN) AF: 0.337 AC: 3535 AN: 10490

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.325 AC: 22076 AN: 67930

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.301 Hom.: 11939

Bravo AF: 0.255

Asia WGS AF: 0.219 AC: 760 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.66
PhyloP100		-0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4509146; hg19: chr6-129955487;