chr6-129627053-T-C

Variant names:

• chr6-129627053-T-C
• rs9375641
• NM_033515.3:c.786+2300A>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.786+2300A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,848 control chromosomes in the GnomAD database, including 14,580 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 0.43 (14580 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.478 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP18	NM_033515.3	MANE Select	c.786+2300A>G		intron	N/A	NP_277050.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP18	ENST00000368149.3	TSL:1 MANE Select	c.786+2300A>G		intron	N/A	ENSP00000357131.2	Q8N392-1
	ARHGAP18	ENST00000909755.1		c.699+2387A>G		intron	N/A	ENSP00000579814.1
	ARHGAP18	ENST00000938085.1		c.786+2300A>G		intron	N/A	ENSP00000608144.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65631 AN: 151730 Hom.: 14553 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.433 AC: 65704 AN: 151848 Hom.: 14580 Cov.: 32 AF XY: 0.430 AC XY: 31921 AN XY: 74224

African (AFR) AF: 0.483 AC: 20021 AN: 41414

American (AMR) AF: 0.390 AC: 5945 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1344 AN: 3464

East Asian (EAS) AF: 0.282 AC: 1460 AN: 5170

South Asian (SAS) AF: 0.289 AC: 1394 AN: 4816

European-Finnish (FIN) AF: 0.455 AC: 4797 AN: 10540

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29351 AN: 67882

Other (OTH) AF: 0.457 AC: 960 AN: 2102

Alfa AF: 0.427 Hom.: 10126

Bravo AF: 0.431

Asia WGS AF: 0.324 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.039
DANN	Benign	0.49
PhyloP100		-2.1
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: rs9375641; hg19: chr6-129948198;