Variant 4-152829707-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001025595.3(ARFIP1):c.74G>A(p.Arg25His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,456,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

ARFIP1
NM_001025595.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.368

Variant links:

Genes affected

ARFIP1 (HGNC:21496): (ADP ribosylation factor interacting protein 1) Enables phosphatidylinositol-4-phosphate binding activity. Involved in negative regulation of retrograde transport, endosome to Golgi. Acts upstream of or within intracellular protein transport and regulation of protein secretion. Located in Golgi membrane; cytosol; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARFIP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0388214).

BP6

Variant 4-152829707-G-A is Benign according to our data. Variant chr4-152829707-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2318652.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFIP1	NM_001025595.3 linkuse as main transcript	c.74G>A	p.Arg25His	missense_variant	2/9	ENST00000353617.7	NP_001020766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFIP1	ENST00000353617.7 linkuse as main transcript	c.74G>A	p.Arg25His	missense_variant	2/9	5	NM_001025595.3	ENSP00000296557	P1	P53367-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249378

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

134902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000274

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000453

AC:

AN:

1456458

Hom.:

Cov.:

AF XY:

0.0000497

AC XY:

AN XY:

724656

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000354

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000442

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000412

AC:

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 specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.1

DANN

Benign

0.79

DEOGEN2

Benign

0.0047

T;T;.;.;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.0079

LIST_S2

Benign

0.45

T;.;T;.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.039

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

N;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

0.69

N;N;N;N;N

REVEL

Benign

0.098

Sift

Benign

0.47

T;T;D;T;T

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.0

B;B;.;.;.

Vest4

0.18

MutPred

0.22

Gain of glycosylation at S28 (P = 0.006);Gain of glycosylation at S28 (P = 0.006);Gain of glycosylation at S28 (P = 0.006);Gain of glycosylation at S28 (P = 0.006);Gain of glycosylation at S28 (P = 0.006);

MVP

0.79

MPC

0.34

ClinPred

0.075

GERP RS

3.0

Varity_R

0.018

gMVP

0.14

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