6-129608064-GAAAAAAAA-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_033515.3(ARHGAP18):c.1123-20_1123-13del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000427 in 984,288 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00046 (0 hom.)
• Consequence: ARHGAP18 NM_033515.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.764

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 6-129608064-GAAAAAAAA-G is Benign according to our data. Variant chr6-129608064-GAAAAAAAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 3039265.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP18	NM_033515.3	c.1123-20_1123-13del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000368149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.1123-20_1123-13del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_033515.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000121 AC: 1 AN: 82640 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000142

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000465 AC: 419 AN: 901648 Hom.: 0 AF XY: 0.000484 AC XY: 209 AN XY: 431990

Gnomad4 AFR exome AF: 0.00144

Gnomad4 AMR exome AF: 0.00252

Gnomad4 ASJ exome AF: 0.00148

Gnomad4 EAS exome AF: 0.00169

Gnomad4 SAS exome AF: 0.00116

Gnomad4 FIN exome AF: 0.00127

Gnomad4 NFE exome AF: 0.000325

Gnomad4 OTH exome AF: 0.000621

GnomAD4 genome AF: 0.0000121 AC: 1 AN: 82640 Hom.: 0 Cov.: 0 AF XY: 0.0000264 AC XY: 1 AN XY: 37912

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000142

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ARHGAP18-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 29, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs577070164; hg19: chr6-129929209;