rs17057678

Variant names:

• chr6-129710348-T-C
• rs17057678
• NM_033515.3:c.-212A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-129710348-T-C
• chr6-129710348-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033515.3(ARHGAP18):​c.-212A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 486,954 control chromosomes in the GnomAD database, including 2,015 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 0.069 (539 hom., cov: 32)
  • Exomes 𝑓: 0.081 (1476 hom.)
• Consequence: ARHGAP18 NM_033515.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• Publications: 10 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 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.-212A>G		upstream_gene	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.-212A>G		upstream_gene	N/A	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.0688 AC: 10469 AN: 152126 Hom.: 538 Cov.: 32

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0658

Gnomad OTH AF: 0.0579

GnomAD4 exome AF: 0.0813 AC: 27228 AN: 334710 Hom.: 1476 AF XY: 0.0821 AC XY: 14233 AN XY: 173438

African (AFR) AF: 0.0201 AC: 215 AN: 10718

American (AMR) AF: 0.0722 AC: 1061 AN: 14702

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 766 AN: 10760

East Asian (EAS) AF: 0.195 AC: 5251 AN: 26866

South Asian (SAS) AF: 0.105 AC: 2744 AN: 26078

European-Finnish (FIN) AF: 0.123 AC: 2867 AN: 23368

Middle Eastern (MID) AF: 0.0332 AC: 50 AN: 1508

European-Non Finnish (NFE) AF: 0.0637 AC: 12767 AN: 200318

Other (OTH) AF: 0.0739 AC: 1507 AN: 20392

GnomAD4 genome AF: 0.0687 AC: 10466 AN: 152244 Hom.: 539 Cov.: 32 AF XY: 0.0758 AC XY: 5639 AN XY: 74434

African (AFR) AF: 0.0222 AC: 924 AN: 41570

American (AMR) AF: 0.0917 AC: 1403 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1220 AN: 5162

South Asian (SAS) AF: 0.121 AC: 584 AN: 4832

European-Finnish (FIN) AF: 0.132 AC: 1392 AN: 10584

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0658 AC: 4476 AN: 68008

Other (OTH) AF: 0.0601 AC: 127 AN: 2112

Alfa AF: 0.0600 Hom.: 542

Bravo AF: 0.0622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.0
DANN	Benign	0.65
PhyloP100		-0.40
PromoterAI		0.034	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17057678; hg19: chr6-130031493;