11-72686155-C-T

Position:

• chr11-72686155-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001040118.3(ARAP1):​c.4222G>A​(p.Val1408Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,613,864 control chromosomes in the GnomAD database, including 277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (245 hom.)
• Consequence: ARAP1 NM_001040118.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.75

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017605126).
• BP6: Variant 11-72686155-C-T is Benign according to our data. Variant chr11-72686155-C-T is described in ClinVar as [Benign]. Clinvar id is 770219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARAP1	NM_001040118.3	c.4222G>A	p.Val1408Met	missense_variant	34/35	ENST00000393609.8	NP_001035207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARAP1	ENST00000393609.8	c.4222G>A	p.Val1408Met	missense_variant	34/35	2	NM_001040118.3	ENSP00000377233.3

Frequencies

GnomAD3 genomes AF: 0.00771 AC: 1173 AN: 152164 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0817

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.0120 AC: 3007 AN: 250486 Hom.: 117 AF XY: 0.0103 AC XY: 1399 AN XY: 135560

Gnomad AFR exome AF: 0.000930

Gnomad AMR exome AF: 0.0365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0875

Gnomad SAS exome AF: 0.00180

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00850

GnomAD4 exome AF: 0.00404 AC: 5910 AN: 1461582 Hom.: 245 Cov.: 33 AF XY: 0.00376 AC XY: 2732 AN XY: 727106

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.0377

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0853

Gnomad4 SAS exome AF: 0.00214

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.00816

GnomAD4 genome AF: 0.00770 AC: 1172 AN: 152282 Hom.: 32 Cov.: 32 AF XY: 0.00882 AC XY: 657 AN XY: 74460

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0819

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00135 Hom.: 2

Bravo AF: 0.0102

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000682 AC: 3

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00946 AC: 1148

Asia WGS AF: 0.0410 AC: 143 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	.;T;.;.;T;T;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.051
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D;D
MetaRNN	Benign	0.0018	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	.;.;.;.;N;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.19	N;.;N;N;N;N;N;N
REVEL	Benign	0.081
Sift	Benign	0.098	T;.;T;T;T;T;T;T
Sift4G	Benign	0.46	T;T;T;T;T;T;T;D
Polyphen		0.16	B;.;B;.;B;B;.;.
Vest4		0.20
MPC		0.34
ClinPred		0.015	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.074
gMVP		0.38

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

Other links and lift over

dbSNP: rs2291288; hg19: chr11-72397200; COSMIC: COSV61990778; COSMIC: COSV61990778;