rs1510653

Positions:

• chr4-36013511-T-C
• chr4-36013511-T-G

Variant summary

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

The ENST00000503225.5(ARAP2):​n.1057-680A>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 0.166 in 152,030 control chromosomes in the GnomAD database, including 4,599 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 0.17 (4599 hom., cov: 32)
• Consequence: ARAP2 ENST00000503225.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARAP2	NR_146893.2	n.5646-680A>G		intron_variant, non_coding_transcript_variant
ARAP2	XR_001741112.3	n.5734-680A>G		intron_variant, non_coding_transcript_variant
ARAP2	XR_001741123.2	n.3785-680A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARAP2	ENST00000503225.5	n.1057-680A>G		intron_variant, non_coding_transcript_variant		1
ARAP2	ENST00000513032.2	n.57-680A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25129 AN: 151912 Hom.: 4588 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.00828

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.166 AC: 25192 AN: 152030 Hom.: 4599 Cov.: 32 AF XY: 0.162 AC XY: 12005 AN XY: 74330

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.0835

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.00830

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0582

Gnomad4 NFE AF: 0.0532

Gnomad4 OTH AF: 0.146

Alfa AF: 0.0647 Hom.: 1467

Bravo AF: 0.181

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1510653; hg19: chr4-36015133;