chr6-129637952-C-T

Variant names:

• chr6-129637952-C-T
• rs9402155
• NM_033515.3:c.552+442G>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.552+442G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,180 control chromosomes in the GnomAD database, including 3,077 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 0.19 (3077 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• 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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.552+442G>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.552+442G>A		intron_variant	Intron 3 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28830 AN: 152062 Hom.: 3074 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.190 AC: 28842 AN: 152180 Hom.: 3077 Cov.: 32 AF XY: 0.190 AC XY: 14145 AN XY: 74400

African (AFR) AF: 0.0957 AC: 3973 AN: 41532

American (AMR) AF: 0.204 AC: 3116 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 647 AN: 3470

East Asian (EAS) AF: 0.157 AC: 815 AN: 5178

South Asian (SAS) AF: 0.187 AC: 901 AN: 4820

European-Finnish (FIN) AF: 0.251 AC: 2657 AN: 10574

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16034 AN: 68008

Other (OTH) AF: 0.206 AC: 436 AN: 2112

Alfa AF: 0.216 Hom.: 11528

Bravo AF: 0.179

Asia WGS AF: 0.194 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		1.6
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: rs9402155; hg19: chr6-129959097; COSMIC: COSV63763806;