rs354706

Positions:

• chr2-143128647-C-T

Variant summary

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

The ENST00000409869.5(ARHGAP15):​c.-14-26830C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,976 control chromosomes in the GnomAD database, including 20,024 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 0.49 (20024 hom., cov: 32)
• Consequence: ARHGAP15 ENST00000409869.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.36

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP15	ENST00000409869.5	c.-14-26830C>T		intron_variant		5		ENSP00000386560

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75159 AN: 151858 Hom.: 20017 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.495 AC: 75197 AN: 151976 Hom.: 20024 Cov.: 32 AF XY: 0.491 AC XY: 36506 AN XY: 74290

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.518

Alfa AF: 0.579 Hom.: 43519

Bravo AF: 0.487

Asia WGS AF: 0.262 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.056
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs354706; hg19: chr2-143886216; COSMIC: COSV54523936; COSMIC: COSV54523936;