rs145513915

Variant names:

• chr4-36091884-C-T
• rs145513915
• NM_015230.4:c.4422G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_015230.4(ARAP2):​c.4422G>A​(p.Val1474Val) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.553
• Publications: 1 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: Benign. The variant received -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 VariationId 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

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.4422G>A	p.Val1474Val	synonymous	Exon 28 of 33	NP_056045.2
	ARAP2	NR_146893.2		n.4912G>A		non_coding_transcript_exon	Exon 28 of 37
	ARAP2	NR_146894.2		n.4883G>A		non_coding_transcript_exon	Exon 28 of 33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP2	ENST00000303965.9	TSL:1 MANE Select	c.4422G>A	p.Val1474Val	synonymous	Exon 28 of 33	ENSP00000302895.4	Q8WZ64
	ARAP2	ENST00000942324.1		c.4422G>A	p.Val1474Val	synonymous	Exon 28 of 33	ENSP00000612383.1
	ARAP2	ENST00000905954.1		c.4353G>A	p.Val1451Val	synonymous	Exon 27 of 32	ENSP00000576013.1

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152150 Hom.: 3 Cov.: 32

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

GnomAD2 exomes AF: 0.000550 AC: 137 AN: 248894 AF XY: 0.000639

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 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.: 6 Cov.: 30 AF XY: 0.000512 AC XY: 368 AN XY: 718880

African (AFR) AF: 0.000813 AC: 27 AN: 33190

American (AMR) AF: 0.00122 AC: 54 AN: 44190

Ashkenazi Jewish (ASJ) AF: 0.000661 AC: 17 AN: 25710

East Asian (EAS) AF: 0.00 AC: 0 AN: 39286

South Asian (SAS) AF: 0.000424 AC: 36 AN: 85002

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52896

Middle Eastern (MID) AF: 0.0159 AC: 88 AN: 5548

European-Non Finnish (NFE) AF: 0.000382 AC: 421 AN: 1102146

Other (OTH) AF: 0.00117 AC: 70 AN: 59746

GnomAD4 genome AF: 0.000630 AC: 96 AN: 152268 Hom.: 3 Cov.: 32 AF XY: 0.000725 AC XY: 54 AN XY: 74436

African (AFR) AF: 0.000385 AC: 16 AN: 41568

American (AMR) AF: 0.00209 AC: 32 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000471 AC: 32 AN: 68012

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000417 Hom.: 0

Bravo AF: 0.000865

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.0
DANN	Benign	0.62
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism

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: rs145513915; hg19: chr4-36093506;