rs1552224

Positions:

• chr11-72722053-A-C

Variant summary

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

The ENST00000334211.12(ARAP1):​c.-430T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 985,342 control chromosomes in the GnomAD database, including 11,185 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 0.12 (1384 hom., cov: 32)
  • Exomes 𝑓: 0.15 (9801 hom.)
• Consequence: ARAP1 ENST00000334211.12 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700

Genes affected

ARAP1 (HGNC:16925): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1) The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARAP1	NM_001040118.3	c.509+4567T>G		intron_variant		ENST00000393609.8	NP_001035207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARAP1	ENST00000393609.8	c.509+4567T>G		intron_variant		2	NM_001040118.3	ENSP00000377233	P3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17747 AN: 151984 Hom.: 1388 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0822

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.0972

GnomAD4 exome AF: 0.151 AC: 125444 AN: 833242 Hom.: 9801 Cov.: 28 AF XY: 0.152 AC XY: 58539 AN XY: 384804

Gnomad4 AFR exome AF: 0.0169

Gnomad4 AMR exome AF: 0.0986

Gnomad4 ASJ exome AF: 0.0873

Gnomad4 EAS exome AF: 0.0590

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.117 AC: 17743 AN: 152100 Hom.: 1384 Cov.: 32 AF XY: 0.123 AC XY: 9116 AN XY: 74364

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0822

Gnomad4 EAS AF: 0.0726

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.0976

Alfa AF: 0.138 Hom.: 3640

Bravo AF: 0.0986

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs1552224; hg19: chr11-72433098;