chr6-129706175-G-A

Variant names:

• chr6-129706175-G-A
• rs2032533
• NM_033515.3:c.113+3849C>T

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+3849C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,122 control chromosomes in the GnomAD database, including 36,071 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 0.69 (36071 hom., cov: 33)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.113+3849C>T		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.113+3849C>T		intron_variant	Intron 1 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104525 AN: 152004 Hom.: 36045 Cov.: 33

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.688 AC: 104602 AN: 152122 Hom.: 36071 Cov.: 33 AF XY: 0.691 AC XY: 51389 AN XY: 74360

African (AFR) AF: 0.629 AC: 26072 AN: 41468

American (AMR) AF: 0.687 AC: 10512 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2306 AN: 3468

East Asian (EAS) AF: 0.646 AC: 3347 AN: 5178

South Asian (SAS) AF: 0.781 AC: 3771 AN: 4826

European-Finnish (FIN) AF: 0.768 AC: 8119 AN: 10570

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48213 AN: 67996

Other (OTH) AF: 0.663 AC: 1401 AN: 2114

Alfa AF: 0.696 Hom.: 67127

Bravo AF: 0.675

Asia WGS AF: 0.677 AC: 2356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.56
PhyloP100		0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=13/87	disease causing

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: rs2032533; hg19: chr6-130027320; COSMIC: COSV63763920;