4-36009740-C-T

Variant names:

• chr4-36009740-C-T
• rs10010285
• ENST00000503225.5:n.1326-2694G>A

Variant summary

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

The ENST00000503225.5(ARAP2):​n.1326-2694G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,850 control chromosomes in the GnomAD database, including 34,731 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 0.67 (34731 hom., cov: 31)
• Consequence: ARAP2 ENST00000503225.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAP2	NR_146893.2	n.5915-2694G>A		intron_variant	Intron 36 of 36
ARAP2	XR_001741112.3	n.6003-2694G>A		intron_variant	Intron 38 of 38
ARAP2	XR_001741123.2	n.4054-2694G>A		intron_variant	Intron 30 of 30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARAP2	ENST00000503225.5	n.1326-2694G>A		intron_variant	Intron 9 of 12	1
ARAP2	ENST00000513032.2	n.326-2694G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102363 AN: 151732 Hom.: 34702 Cov.: 31

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.675 AC: 102440 AN: 151850 Hom.: 34731 Cov.: 31 AF XY: 0.681 AC XY: 50499 AN XY: 74180

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.646

Alfa AF: 0.632 Hom.: 58651

Bravo AF: 0.684

Asia WGS AF: 0.697 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10010285; hg19: chr4-36011362;