rs17457078

Positions:

• chr4-36152010-T-C

Variant summary

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

The NM_015230.4(ARAP2):​c.2753-966A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,142 control chromosomes in the GnomAD database, including 5,056 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 0.24 (5056 hom., cov: 32)
• Consequence: ARAP2 NM_015230.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

Genes affected

ARAP2 (HGNC:16924): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2) The protein encoded by this gene contains ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology domains. The protein is a phosphatidylinositol (3,4,5)-trisphosphate-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RHO-GAP domain and does not have RHO-GAP activity. The protein associates with focal adhesions and functions downstream of RhoA to regulate focal adhesion dynamics. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARAP2	NM_015230.4	c.2753-966A>G		intron_variant		ENST00000303965.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARAP2	ENST00000303965.9	c.2753-966A>G		intron_variant		1	NM_015230.4	P1
ARAP2	ENST00000512804.1	n.547-966A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36918 AN: 152024 Hom.: 5055 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.0793

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.243 AC: 36930 AN: 152142 Hom.: 5056 Cov.: 32 AF XY: 0.239 AC XY: 17756 AN XY: 74372

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.0797

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.256

Alfa AF: 0.296 Hom.: 2988

Bravo AF: 0.234

Asia WGS AF: 0.195 AC: 682 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.71

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: rs17457078; hg19: chr4-36153632; COSMIC: COSV58291491;