rs79464052

chr5-141655607-G-C

Variant summary

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

The NM_022481.6(ARAP3):c.4110+14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 1,613,850 control chromosomes in the GnomAD database, including 4,009 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 0.077 (491 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3518 hom.)
• Consequence: ARAP3 NM_022481.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

Genes affected

ARAP3 (HGNC:24097): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3) This gene encodes a phosphoinositide binding protein containing ARF-GAP, RHO-GAP, RAS-associating, and pleckstrin homology domains. The ARF-GAP and RHO-GAP domains cooperate in mediating rearrangements in the cell cytoskeleton and cell shape. It is a specific PtdIns(3,4,5)P3/PtdIns(3,4)P2-stimulated Arf6-GAP protein. An alternatively spliced transcript has been found for this gene, but its biological validity has not been determined. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARAP3	NM_022481.6	c.4110+14C>G		intron_variant		ENST00000239440.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARAP3	ENST00000239440.9	c.4110+14C>G		intron_variant		1	NM_022481.6	P1

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 11783 AN: 152076 Hom.: 493 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0880

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0619

Gnomad OTH AF: 0.0989

GnomAD3 exomes AF: 0.0712 AC: 17869 AN: 251012 Hom.: 759 AF XY: 0.0739 AC XY: 10035 AN XY: 135708

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.0382

Gnomad ASJ exome AF: 0.0945

Gnomad EAS exome AF: 0.0451

Gnomad SAS exome AF: 0.126

Gnomad FIN exome AF: 0.0828

Gnomad NFE exome AF: 0.0617

Gnomad OTH exome AF: 0.0685

GnomAD4 exome AF: 0.0646 AC: 94414 AN: 1461656 Hom.: 3518 Cov.: 35 AF XY: 0.0667 AC XY: 48465 AN XY: 727122

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0414

Gnomad4 ASJ exome AF: 0.0921

Gnomad4 EAS exome AF: 0.0336

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0811

Gnomad4 NFE exome AF: 0.0585

Gnomad4 OTH exome AF: 0.0741

GnomAD4 genome AF: 0.0775 AC: 11795 AN: 152194 Hom.: 491 Cov.: 32 AF XY: 0.0793 AC XY: 5904 AN XY: 74414

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0523

Gnomad4 ASJ AF: 0.0982

Gnomad4 EAS AF: 0.0478

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0880

Gnomad4 NFE AF: 0.0619

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0709 Hom.: 81

Bravo AF: 0.0740

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.5
Dann	Benign	0.46

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: rs79464052; hg19: chr5-141035174; COSMIC: COSV53351133; COSMIC: COSV53351133;