6-129634182-T-C

Variant names:

• chr6-129634182-T-C
• rs12664247
• NM_033515.3:c.553-77A>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.553-77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,300,260 control chromosomes in the GnomAD database, including 59,814 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 0.27 (5849 hom., cov: 31)
  • Exomes 𝑓: 0.30 (53965 hom.)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• 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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.553-77A>G		intron_variant	Intron 3 of 14	ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.553-77A>G		intron_variant	Intron 3 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40539 AN: 151902 Hom.: 5842 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.298 AC: 342281 AN: 1148240 Hom.: 53965 AF XY: 0.297 AC XY: 173195 AN XY: 583564

African (AFR) AF: 0.164 AC: 4391 AN: 26732

American (AMR) AF: 0.222 AC: 8902 AN: 40152

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7014 AN: 23340

East Asian (EAS) AF: 0.166 AC: 6304 AN: 38044

South Asian (SAS) AF: 0.222 AC: 16943 AN: 76470

European-Finnish (FIN) AF: 0.349 AC: 17929 AN: 51408

Middle Eastern (MID) AF: 0.313 AC: 1579 AN: 5048

European-Non Finnish (NFE) AF: 0.316 AC: 264520 AN: 837240

Other (OTH) AF: 0.295 AC: 14699 AN: 49806

GnomAD4 genome AF: 0.267 AC: 40570 AN: 152020 Hom.: 5849 Cov.: 31 AF XY: 0.266 AC XY: 19745 AN XY: 74314

African (AFR) AF: 0.163 AC: 6750 AN: 41478

American (AMR) AF: 0.279 AC: 4258 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3470

East Asian (EAS) AF: 0.169 AC: 876 AN: 5176

South Asian (SAS) AF: 0.235 AC: 1135 AN: 4824

European-Finnish (FIN) AF: 0.334 AC: 3525 AN: 10544

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22079 AN: 67946

Other (OTH) AF: 0.295 AC: 624 AN: 2114

Alfa AF: 0.301 Hom.: 14571

Bravo AF: 0.257

Asia WGS AF: 0.219 AC: 761 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.90
PhyloP100		0.30
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: rs12664247; hg19: chr6-129955327;