chr6-129600071-G-A

Variant names:

• chr6-129600071-G-A
• rs9321174
• NM_033515.3:c.1572+571C>T

Variant summary

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

The NM_033515.3(ARHGAP18):​c.1572+571C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,878 control chromosomes in the GnomAD database, including 7,708 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 0.31 (7708 hom., cov: 32)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• Publications: 9 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.1572+571C>T		intron_variant	Intron 11 of 14	ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.1572+571C>T		intron_variant	Intron 11 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47572 AN: 151760 Hom.: 7698 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.314 AC: 47637 AN: 151878 Hom.: 7708 Cov.: 32 AF XY: 0.315 AC XY: 23346 AN XY: 74232

African (AFR) AF: 0.253 AC: 10464 AN: 41422

American (AMR) AF: 0.354 AC: 5392 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3466

East Asian (EAS) AF: 0.130 AC: 674 AN: 5180

South Asian (SAS) AF: 0.203 AC: 977 AN: 4808

European-Finnish (FIN) AF: 0.382 AC: 4015 AN: 10510

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24216 AN: 67938

Other (OTH) AF: 0.319 AC: 673 AN: 2108

Alfa AF: 0.340 Hom.: 30039

Bravo AF: 0.311

Asia WGS AF: 0.207 AC: 716 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.89
DANN	Benign	0.26
PhyloP100		0.24
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: rs9321174; hg19: chr6-129921216;