chr6-129585508-T-C

Position:

• chr6-129585508-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033515.3(ARHGAP18):​c.1714-1396A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,030 control chromosomes in the GnomAD database, including 4,680 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 0.23 (4680 hom., cov: 31)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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]

ARHGAP18 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.1714-1396A>G		intron_variant		ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.1714-1396A>G		intron_variant		1	NM_033515.3	ENSP00000357131.2
ARHGAP18	ENST00000463225.1	n.92-1396A>G		intron_variant		3
ARHGAP18	ENST00000483367.5	n.88-1396A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35267 AN: 151914 Hom.: 4681 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.0617

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.232 AC: 35292 AN: 152030 Hom.: 4680 Cov.: 31 AF XY: 0.228 AC XY: 16921 AN XY: 74302

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.0618

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.249

Alfa AF: 0.292 Hom.: 9009

Bravo AF: 0.223

Asia WGS AF: 0.113 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.042
DANN	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs9492347; hg19: chr6-129906653;