rs4479964

Variant names:

• chr6-129650399-G-A
• rs4479964
• NM_033515.3:c.114-8381C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-129650399-G-A
• chr6-129650399-G-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.114-8381C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,918 control chromosomes in the GnomAD database, including 8,967 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 0.34 (8967 hom., cov: 31)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.114-8381C>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.114-8381C>T		intron_variant	Intron 1 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51676 AN: 151800 Hom.: 8955 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.340 AC: 51725 AN: 151918 Hom.: 8967 Cov.: 31 AF XY: 0.340 AC XY: 25255 AN XY: 74264

African (AFR) AF: 0.344 AC: 14265 AN: 41412

American (AMR) AF: 0.315 AC: 4813 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3468

East Asian (EAS) AF: 0.353 AC: 1819 AN: 5160

South Asian (SAS) AF: 0.325 AC: 1567 AN: 4818

European-Finnish (FIN) AF: 0.329 AC: 3472 AN: 10550

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23417 AN: 67942

Other (OTH) AF: 0.364 AC: 766 AN: 2106

Alfa AF: 0.342 Hom.: 16444

Bravo AF: 0.339

Asia WGS AF: 0.369 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.46
PhyloP100		-0.19
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: rs4479964; hg19: chr6-129971544;