4-36009740-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000503225.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP2	NR_146893.2		n.5915-2694G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP2	ENST00000503225.5	TSL:1	n.1326-2694G>A		intron	N/A
	ARAP2	ENST00000513032.2	TSL:3	n.326-2694G>A		intron	N/A

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

African (AFR) AF: 0.717 AC: 29693 AN: 41398

American (AMR) AF: 0.768 AC: 11708 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1998 AN: 3468

East Asian (EAS) AF: 0.727 AC: 3758 AN: 5170

South Asian (SAS) AF: 0.668 AC: 3221 AN: 4824

European-Finnish (FIN) AF: 0.704 AC: 7424 AN: 10544

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42456 AN: 67890

Other (OTH) AF: 0.646 AC: 1364 AN: 2112

Alfa AF: 0.640 Hom.: 95672

Bravo AF: 0.684

Asia WGS AF: 0.697 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.18
PhyloP100		0.25

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10010285;

hg19: chr4-36011362;