4-36077972-T-C

Variant names:

• chr4-36077972-T-C
• rs12651329
• NM_015230.4:c.4608+2244A>G

Variant summary

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

The NM_015230.4(ARAP2):​c.4608+2244A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,922 control chromosomes in the GnomAD database, including 16,187 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 0.46 (16187 hom., cov: 31)
• Consequence: ARAP2 NM_015230.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015230.4. 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	NM_015230.4	MANE Select	c.4608+2244A>G		intron	N/A	NP_056045.2
	ARAP2	NR_146893.2		n.5098+2244A>G		intron	N/A
	ARAP2	NR_146894.2		n.5069+2244A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP2	ENST00000303965.9	TSL:1 MANE Select	c.4608+2244A>G		intron	N/A	ENSP00000302895.4	Q8WZ64
	ARAP2	ENST00000942324.1		c.4608+2244A>G		intron	N/A	ENSP00000612383.1
	ARAP2	ENST00000905954.1		c.4539+2244A>G		intron	N/A	ENSP00000576013.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69227 AN: 151804 Hom.: 16181 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.456 AC: 69274 AN: 151922 Hom.: 16187 Cov.: 31 AF XY: 0.462 AC XY: 34329 AN XY: 74246

African (AFR) AF: 0.492 AC: 20369 AN: 41410

American (AMR) AF: 0.514 AC: 7836 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3237 AN: 5146

South Asian (SAS) AF: 0.388 AC: 1868 AN: 4814

European-Finnish (FIN) AF: 0.566 AC: 5985 AN: 10576

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27452 AN: 67942

Other (OTH) AF: 0.430 AC: 907 AN: 2108

Alfa AF: 0.425 Hom.: 17994

Bravo AF: 0.452

Asia WGS AF: 0.505 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.49
DANN	Benign	0.52
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12651329; hg19: chr4-36079594;