chr11-72685669-C-T

Variant names:

• chr11-72685669-C-T
• rs1855638523
• NM_001040118.3:c.4348G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040118.3(ARAP1):​c.4348G>A​(p.Val1450Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ARAP1 NM_001040118.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.205
• Publications: 0 publications found

Genes affected

ARAP1 (HGNC:16925): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1) The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ARAP1-AS1 (HGNC:39993): (ARAP1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10768205).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040118.3. 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
	ARAP1	NM_001040118.3	MANE Select	c.4348G>A	p.Val1450Ile	missense	Exon 35 of 35	NP_001035207.1	Q96P48-6
	ARAP1	NM_015242.5		c.3613G>A	p.Val1205Ile	missense	Exon 33 of 33	NP_056057.2	Q96P48-4
	ARAP1	NM_001369489.1		c.3580G>A	p.Val1194Ile	missense	Exon 32 of 32	NP_001356418.1	E7EU13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP1	ENST00000393609.8	TSL:2 MANE Select	c.4348G>A	p.Val1450Ile	missense	Exon 35 of 35	ENSP00000377233.3	Q96P48-6
	ARAP1	ENST00000393605.7	TSL:1	c.3628G>A	p.Val1210Ile	missense	Exon 30 of 30	ENSP00000377230.3	Q96P48-1
	ARAP1	ENST00000334211.12	TSL:1	c.3613G>A	p.Val1205Ile	missense	Exon 33 of 33	ENSP00000335506.8	Q96P48-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461732 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727172

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111896

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

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	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.20
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.035
Sift	Uncertain	0.024	D
Sift4G	Pathogenic	0.0	D
MutPred		0.29		Loss of MoRF binding (P = 0.0019)
MVP		0.26
ClinPred		0.29	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.080
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1855638523; hg19: chr11-72396714;