4-36082273-C-T

Variant names:

• chr4-36082273-C-T
• rs141152965
• NM_015230.4:c.4522G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015230.4(ARAP2):​c.4522G>A​(p.Ala1508Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000527 in 1,610,060 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (1 hom.)
• Consequence: ARAP2 NM_015230.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.078894794).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015230.4. 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
	ARAP2	NM_015230.4	MANE Select	c.4522G>A	p.Ala1508Thr	missense	Exon 30 of 33	NP_056045.2
	ARAP2	NR_146893.2		n.5012G>A		non_coding_transcript_exon	Exon 30 of 37
	ARAP2	NR_146894.2		n.4983G>A		non_coding_transcript_exon	Exon 30 of 33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP2	ENST00000303965.9	TSL:1 MANE Select	c.4522G>A	p.Ala1508Thr	missense	Exon 30 of 33	ENSP00000302895.4	Q8WZ64
	ARAP2	ENST00000942324.1		c.4522G>A	p.Ala1508Thr	missense	Exon 30 of 33	ENSP00000612383.1
	ARAP2	ENST00000905954.1		c.4453G>A	p.Ala1485Thr	missense	Exon 29 of 32	ENSP00000576013.1

Frequencies

GnomAD3 genomes AF: 0.000349 AC: 53 AN: 151914 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000633

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000352 AC: 87 AN: 247272 AF XY: 0.000382

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000176

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000537

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000545 AC: 795 AN: 1458028 Hom.: 1 Cov.: 30 AF XY: 0.000518 AC XY: 376 AN XY: 725222

African (AFR) AF: 0.000120 AC: 4 AN: 33316

American (AMR) AF: 0.000202 AC: 9 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.000632 AC: 54 AN: 85506

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53302

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5734

European-Non Finnish (NFE) AF: 0.000623 AC: 692 AN: 1110086

Other (OTH) AF: 0.000465 AC: 28 AN: 60152

GnomAD4 genome AF: 0.000349 AC: 53 AN: 152032 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74302

African (AFR) AF: 0.0000964 AC: 4 AN: 41480

American (AMR) AF: 0.0000656 AC: 1 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000633 AC: 43 AN: 67976

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000532 Hom.: 1

Bravo AF: 0.000329

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000354 AC: 43

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.12
Sift	Benign	0.23	T
Sift4G	Benign	0.19	T
Polyphen		0.92	P
Vest4		0.55
MVP		0.32
MPC		0.029
ClinPred		0.13	T
GERP RS		6.0
Varity_R		0.13
gMVP		0.29
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs141152965; hg19: chr4-36083895;