rs4662198

chr2-143290158-G-T

Variant summary

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

The NM_018460.4(ARHGAP15):c.474+39558G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,014 control chromosomes in the GnomAD database, including 4,167 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 0.22 (4167 hom., cov: 31)
• Consequence: ARHGAP15 NM_018460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

Genes affected

ARHGAP15 (HGNC:21030): (Rho GTPase activating protein 15) RHO GTPases (see ARHA; MIM 165390) regulate diverse biologic processes, and their activity is regulated by RHO GTPase-activating proteins (GAPs), such as ARHGAP15 (Seoh et al., 2003 [PubMed 12650940]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP15	NM_018460.4	c.474+39558G>T		intron_variant		ENST00000295095.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP15	ENST00000295095.11	c.474+39558G>T		intron_variant		1	NM_018460.4	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33316 AN: 151894 Hom.: 4164 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.219 AC: 33340 AN: 152014 Hom.: 4167 Cov.: 31 AF XY: 0.226 AC XY: 16777 AN XY: 74290

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.244

Alfa AF: 0.231 Hom.: 5861

Bravo AF: 0.231

Asia WGS AF: 0.352 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.2
Dann	Benign	0.54

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: rs4662198; hg19: chr2-144047727;