Genetic Variant ARAP3:c.4150-121A>T (chr5-141654556-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

7 publications found

Variant links:

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]

ARAP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022481.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP3	NM_022481.6	MANE Select	c.4150-121A>T		intron	N/A	NP_071926.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARAP3	ENST00000239440.9	TSL:1 MANE Select	c.4150-121A>T	intron	N/A	ENSP00000239440.4
ARAP3	ENST00000508305.5	TSL:2	c.3643-121A>T	intron	N/A	ENSP00000421826.1
ARAP3	ENST00000626478.2	TSL:5	c.3643-121A>T	intron	N/A	ENSP00000486980.1

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100664

AN:

151878

Hom.:

33730

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

13557

27114

40672

54229

67786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16780

33560

50340

67120

83900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.663

AC:

100767

AN:

151994

Hom.:

33777

Cov.:

AF XY:

0.662

AC XY:

49142

AN XY:

74284

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1706

3413

5119

6826

8532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.29

(source)

DANN

Benign

0.40

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over