rs11728293

Variant names:

• chr4-35999959-T-C
• rs11728293
• ENST00000503225.5:n.1469+6944A>G

Variant summary

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

The ENST00000503225.5(ARAP2):​n.1469+6944A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 152,266 control chromosomes in the GnomAD database, including 182 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 0.045 (182 hom., cov: 33)
• Consequence: ARAP2 ENST00000503225.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0675 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
ARAP2	ENST00000503225.5	n.1469+6944A>G		intron_variant	Intron 10 of 12	1

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6831 AN: 152148 Hom.: 182 Cov.: 33

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0378

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

GnomAD4 genome AF: 0.0449 AC: 6830 AN: 152266 Hom.: 182 Cov.: 33 AF XY: 0.0438 AC XY: 3263 AN XY: 74452

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.0272

Gnomad4 ASJ AF: 0.0351

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0607

Gnomad4 NFE AF: 0.0691

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0599 Hom.: 158

Bravo AF: 0.0415

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11728293; hg19: chr4-36001581;