6-129636586-T-C

Variant names:

• chr6-129636586-T-C
• rs4310078
• NM_033515.3:c.552+1808A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_033515.3(ARHGAP18):​c.552+1808A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 152,248 control chromosomes in the GnomAD database, including 425 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 0.062 (425 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.552+1808A>G		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+1808A>G		intron_variant	Intron 3 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9437 AN: 152130 Hom.: 425 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0664

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0883

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0620 AC: 9445 AN: 152248 Hom.: 425 Cov.: 32 AF XY: 0.0609 AC XY: 4533 AN XY: 74432

African (AFR) AF: 0.0177 AC: 737 AN: 41554

American (AMR) AF: 0.0664 AC: 1015 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0496 AC: 239 AN: 4820

European-Finnish (FIN) AF: 0.0839 AC: 890 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0883 AC: 6004 AN: 67996

Other (OTH) AF: 0.0743 AC: 157 AN: 2114

Alfa AF: 0.0715 Hom.: 77

Bravo AF: 0.0599

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.79
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4310078; hg19: chr6-129957731;