NM_033515.3:c.113+22237T>C

Variant names:

• chr6-129687787-A-G
• rs2051632
• NM_033515.3:c.113+22237T>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.113+22237T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 145,504 control chromosomes in the GnomAD database, including 18,764 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 0.52 (18764 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.565 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.113+22237T>C		intron	N/A	NP_277050.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP18	ENST00000368149.3	TSL:1 MANE Select	c.113+22237T>C		intron	N/A	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.516 AC: 74999 AN: 145390 Hom.: 18755 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.516 AC: 75053 AN: 145504 Hom.: 18764 Cov.: 32 AF XY: 0.517 AC XY: 36836 AN XY: 71252

African (AFR) AF: 0.475 AC: 19284 AN: 40580

American (AMR) AF: 0.575 AC: 8561 AN: 14890

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1675 AN: 3260

East Asian (EAS) AF: 0.444 AC: 2278 AN: 5136

South Asian (SAS) AF: 0.539 AC: 2305 AN: 4274

European-Finnish (FIN) AF: 0.528 AC: 5402 AN: 10228

Middle Eastern (MID) AF: 0.565 AC: 157 AN: 278

European-Non Finnish (NFE) AF: 0.528 AC: 33766 AN: 63942

Other (OTH) AF: 0.515 AC: 1040 AN: 2020

Alfa AF: 0.503 Hom.: 29504

Bravo AF: 0.503

Asia WGS AF: 0.432 AC: 1496 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.52
PhyloP100		-0.031
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: rs2051632; hg19: chr6-130008932;