rs6580194

Variant names:

• chr5-141654556-T-A
• rs6580194
• NM_022481.6:c.4150-121A>T

Variant summary

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

The NM_022481.6(ARAP3):​c.4150-121A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 1,399,428 control chromosomes in the GnomAD database, including 294,100 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 0.66 (33777 hom., cov: 31)
  • Exomes 𝑓: 0.64 (260323 hom.)
• Consequence: ARAP3 NM_022481.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAP3	NM_022481.6	c.4150-121A>T		intron_variant	Intron 32 of 32	ENST00000239440.9	NP_071926.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARAP3	ENST00000239440.9	c.4150-121A>T		intron_variant	Intron 32 of 32	1	NM_022481.6	ENSP00000239440.4

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100664 AN: 151878 Hom.: 33730 Cov.: 31

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.643 AC: 801790 AN: 1247434 Hom.: 260323 AF XY: 0.642 AC XY: 394250 AN XY: 614016

African (AFR) AF: 0.715 AC: 20059 AN: 28054

American (AMR) AF: 0.773 AC: 21146 AN: 27370

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 11296 AN: 19148

East Asian (EAS) AF: 0.339 AC: 12933 AN: 38126

South Asian (SAS) AF: 0.649 AC: 43120 AN: 66462

European-Finnish (FIN) AF: 0.669 AC: 23259 AN: 34792

Middle Eastern (MID) AF: 0.618 AC: 2948 AN: 4774

European-Non Finnish (NFE) AF: 0.649 AC: 633333 AN: 976152

Other (OTH) AF: 0.641 AC: 33696 AN: 52556

GnomAD4 genome AF: 0.663 AC: 100767 AN: 151994 Hom.: 33777 Cov.: 31 AF XY: 0.662 AC XY: 49142 AN XY: 74284

African (AFR) AF: 0.718 AC: 29749 AN: 41424

American (AMR) AF: 0.720 AC: 10988 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2062 AN: 3470

East Asian (EAS) AF: 0.333 AC: 1711 AN: 5144

South Asian (SAS) AF: 0.627 AC: 3020 AN: 4820

European-Finnish (FIN) AF: 0.665 AC: 7035 AN: 10574

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.650 AC: 44201 AN: 67992

Other (OTH) AF: 0.678 AC: 1425 AN: 2102

Alfa AF: 0.670 Hom.: 4295

Bravo AF: 0.667

Asia WGS AF: 0.567 AC: 1973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.29
DANN	Benign	0.40
PhyloP100		-1.2
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: rs6580194; hg19: chr5-141034123; COSMIC: COSV53351994; COSMIC: COSV53351994;