NM_033515.3:c.114-30732C>A

Variant names:

• chr6-129672750-G-T
• rs13203608
• NM_033515.3:c.114-30732C>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.114-30732C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 152,266 control chromosomes in the GnomAD database, including 427 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 0.061 (427 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.931
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.114-30732C>A		intron_variant	Intron 1 of 14	ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.114-30732C>A		intron_variant	Intron 1 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9294 AN: 152148 Hom.: 427 Cov.: 32

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0887

Gnomad OTH AF: 0.0767

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

GnomAD4 genome AF: 0.0610 AC: 9292 AN: 152266 Hom.: 427 Cov.: 32 AF XY: 0.0593 AC XY: 4416 AN XY: 74446

African (AFR) AF: 0.0157 AC: 651 AN: 41572

American (AMR) AF: 0.0646 AC: 988 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4824

European-Finnish (FIN) AF: 0.0815 AC: 862 AN: 10582

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0887 AC: 6036 AN: 68016

Other (OTH) AF: 0.0759 AC: 160 AN: 2108

Alfa AF: 0.0821 Hom.: 1189

Bravo AF: 0.0594

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.70
PhyloP100		0.93
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: rs13203608; hg19: chr6-129993895;