Genetic Variant NM_022481.6:c.4110+14C>G (chr5-141655607-G-C) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.255

Publications

12 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP3	NM_022481.6	MANE Select	c.4110+14C>G		intron	N/A	NP_071926.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARAP3	ENST00000239440.9	TSL:1 MANE Select	c.4110+14C>G	intron	N/A	ENSP00000239440.4	Q8WWN8-1
ARAP3	ENST00000955414.1		c.4110+14C>G	intron	N/A	ENSP00000625473.1
ARAP3	ENST00000925545.1		c.4050+14C>G	intron	N/A	ENSP00000595604.1

Frequencies

GnomAD3 genomes

AF:

0.0775

AC:

11783

AN:

152076

Hom.:

493

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0712

AC:

17869

AN:

251012

AF XY:

0.0739

show subpopulations

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 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.:

AF XY:

0.0667

AC XY:

48465

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.108

AC:

3618

AN:

33474

American (AMR)

AF:

0.0414

AC:

1853

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0921

AC:

2407

AN:

26136

East Asian (EAS)

AF:

0.0336

AC:

1334

AN:

39700

South Asian (SAS)

AF:

0.125

AC:

10767

AN:

86244

European-Finnish (FIN)

AF:

0.0811

AC:

4326

AN:

53326

Middle Eastern (MID)

AF:

0.110

AC:

628

AN:

5712

European-Non Finnish (NFE)

AF:

0.0585

AC:

65010

AN:

1111966

Other (OTH)

AF:

0.0741

AC:

4471

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

5143

10285

15428

20570

25713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2486

4972

7458

9944

12430

<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:

0.0775

AC:

11795

AN:

152194

Hom.:

491

Cov.:

AF XY:

0.0793

AC XY:

5904

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.107

AC:

4438

AN:

41496

American (AMR)

AF:

0.0523

AC:

800

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0982

AC:

341

AN:

3472

East Asian (EAS)

AF:

0.0478

AC:

247

AN:

5166

South Asian (SAS)

AF:

0.119

AC:

576

AN:

4828

European-Finnish (FIN)

AF:

0.0880

AC:

933

AN:

10608

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0619

AC:

4209

AN:

68002

Other (OTH)

AF:

0.100

AC:

212

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

571

1142

1714

2285

2856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0709

Hom.:

Bravo

AF:

0.0740

Asia WGS

AF:

0.117

AC:

407

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.5

(source)

DANN

Benign

0.46

PhyloP100

-0.26

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