rs11728293

Positions:

• chr4-35999959-T-C

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, non coding transcript 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, non_coding_transcript
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARAP2	ENST00000503225.5	n.1469+6944A>G		intron_variant, non_coding_transcript_variant		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;