ENST00000503225.5:n.608-5839A>G

Variant names:

• chr4-36025125-T-C
• rs1567482
• ENST00000503225.5:n.608-5839A>G

Variant summary

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

The ENST00000503225.5(ARAP2):​n.608-5839A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,122 control chromosomes in the GnomAD database, including 53,476 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 0.83 (53476 hom., cov: 31)
• Consequence: ARAP2 ENST00000503225.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAP2	NR_146893.2	n.5646-12294A>G		intron_variant	Intron 35 of 36
ARAP2	XR_001741112.3	n.5344-5839A>G		intron_variant	Intron 35 of 38
ARAP2	XR_001741123.2	n.3395-5839A>G		intron_variant	Intron 27 of 30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARAP2	ENST00000503225.5	n.608-5839A>G		intron_variant	Intron 5 of 12	1
ARAP2	ENST00000513032.2	n.57-12294A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126879 AN: 152004 Hom.: 53442 Cov.: 31

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.846

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

GnomAD4 genome AF: 0.835 AC: 126966 AN: 152122 Hom.: 53476 Cov.: 31 AF XY: 0.839 AC XY: 62363 AN XY: 74370

African (AFR) AF: 0.706 AC: 29291 AN: 41460

American (AMR) AF: 0.909 AC: 13874 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3180 AN: 3472

East Asian (EAS) AF: 0.835 AC: 4329 AN: 5184

South Asian (SAS) AF: 0.866 AC: 4172 AN: 4818

European-Finnish (FIN) AF: 0.910 AC: 9641 AN: 10596

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59652 AN: 68008

Other (OTH) AF: 0.836 AC: 1766 AN: 2112

Alfa AF: 0.867 Hom.: 47890

Bravo AF: 0.829

Asia WGS AF: 0.815 AC: 2835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.9
DANN	Benign	0.56
PhyloP100		0.10

Splicing

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

Other links and lift over

dbSNP: rs1567482; hg19: chr4-36026747;