Variant 4-36091884-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015230.4(ARAP2):c.4422G>A(p.Val1474=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000506 in 1,599,982 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00063 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 6 hom. )

Consequence

ARAP2
NM_015230.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.553

Variant links:

Genes affected

ARAP2 (HGNC:16924): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2) The protein encoded by this gene contains ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology domains. The protein is a phosphatidylinositol (3,4,5)-trisphosphate-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RHO-GAP domain and does not have RHO-GAP activity. The protein associates with focal adhesions and functions downstream of RhoA to regulate focal adhesion dynamics. [provided by RefSeq, Sep 2008]

ARAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 4-36091884-C-T is Benign according to our data. Variant chr4-36091884-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654706.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.553 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARAP2	NM_015230.4 linkuse as main transcript	c.4422G>A	p.Val1474=	synonymous_variant	28/33	ENST00000303965.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARAP2	ENST00000303965.9 linkuse as main transcript	c.4422G>A	p.Val1474=	synonymous_variant	28/33	1	NM_015230.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000550

AC:

137

AN:

248894

Hom.:

AF XY:

0.000639

AC XY:

AN XY:

134582

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.000602

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000463

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000532

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.000493

AC:

714

AN:

1447714

Hom.:

Cov.:

AF XY:

0.000512

AC XY:

368

AN XY:

718880

show subpopulations

Gnomad4 AFR exome

AF:

0.000813

Gnomad4 AMR exome

AF:

0.00122

Gnomad4 ASJ exome

AF:

0.000661

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000424

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000382

Gnomad4 OTH exome

AF:

0.00117

GnomAD4 genome

AF:

0.000630

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000417

Hom.:

Bravo

AF:

0.000865

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

ARAP2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.0

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over