rs6834483

Variant names:

• chr4-35981489-C-T
• rs6834483
• ENST00000503225.5:n.1607+3741G>A

Variant summary

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

The ENST00000503225.5(ARAP2):​n.1607+3741G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.973 in 152,272 control chromosomes in the GnomAD database, including 72,165 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 0.97 (72165 hom., cov: 32)
• Consequence: ARAP2 ENST00000503225.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARAP2	ENST00000503225.5	n.1607+3741G>A		intron_variant	Intron 11 of 12	1

Frequencies

GnomAD3 genomes AF: 0.973 AC: 148112 AN: 152154 Hom.: 72113 Cov.: 32

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.967

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

GnomAD4 genome AF: 0.973 AC: 148219 AN: 152272 Hom.: 72165 Cov.: 32 AF XY: 0.975 AC XY: 72548 AN XY: 74442

Gnomad4 AFR AF: 0.985

Gnomad4 AMR AF: 0.977

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.962

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.966

Gnomad4 OTH AF: 0.959

Alfa AF: 0.966 Hom.: 66577

Bravo AF: 0.973

Asia WGS AF: 0.923 AC: 3208 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.49
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6834483; hg19: chr4-35983111;