rs354706

Variant names:

• chr2-143128647-C-T
• rs354706
• ENST00000819966.1:n.451G>A

Variant summary

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

The ENST00000819966.1(ENSG00000306657):​n.451G>A variant causes a non coding transcript exon 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: ENSG00000306657 ENST00000819966.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.36
• Publications: 9 publications found

Genes affected

ENSG00000306657 (HGNC:):

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000306657	ENST00000819966.1	n.451G>A		non_coding_transcript_exon_variant	Exon 2 of 2
ARHGAP15	ENST00000409869.5	c.-14-26830C>T		intron_variant	Intron 2 of 6	5		ENSP00000386560.1

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

African (AFR) AF: 0.319 AC: 13205 AN: 41412

American (AMR) AF: 0.538 AC: 8217 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2048 AN: 3468

East Asian (EAS) AF: 0.246 AC: 1274 AN: 5178

South Asian (SAS) AF: 0.282 AC: 1361 AN: 4818

European-Finnish (FIN) AF: 0.631 AC: 6653 AN: 10548

Middle Eastern (MID) AF: 0.555 AC: 161 AN: 290

European-Non Finnish (NFE) AF: 0.597 AC: 40608 AN: 67970

Other (OTH) AF: 0.518 AC: 1095 AN: 2114

Alfa AF: 0.572 Hom.: 62962

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
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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