Variant rs2736182 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001623.5(AIF1):c.40G>A(p.Gly14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,613,512 control chromosomes in the GnomAD database, including 2,789 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.079 ( 896 hom., cov: 30)

Exomes 𝑓: 0.032 ( 1893 hom. )

Consequence

AIF1
NM_001623.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.49

Variant links:

Genes affected

AIF1 (HGNC:352): (allograft inflammatory factor 1) This gene encodes a protein that binds actin and calcium. This gene is induced by cytokines and interferon and may promote macrophage activation and growth of vascular smooth muscle cells and T-lymphocytes. Polymorphisms in this gene may be associated with systemic sclerosis. Alternative splicing results in multiple transcript variants, but the full-length and coding nature of some of these variants is not certain. [provided by RefSeq, Jan 2016]

AIF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016286075).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AIF1	NM_001623.5 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	2/6	ENST00000376059.8	NP_001614.3
AIF1	XM_005248870.5 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	2/4		XP_005248927.1
AIF1	NM_001318970.2 linkuse as main transcript	c.-123G>A		5_prime_UTR_variant	2/6		NP_001305899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIF1	ENST00000376059.8 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	2/6	1	NM_001623.5	ENSP00000365227	P1	P55008-1
AIF1	ENST00000337917.11 linkuse as main transcript	c.82G>A	p.Gly28Arg	missense_variant	2/6	1		ENSP00000338776
AIF1	ENST00000466820.1 linkuse as main transcript	n.90G>A		non_coding_transcript_exon_variant	2/4	5
AIF1	ENST00000497362.5 linkuse as main transcript	n.92G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.0794

AC:

12041

AN:

151690

Hom.:

896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0720

Gnomad ASJ

AF:

0.0306

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.0700

Gnomad FIN

AF:

0.00538

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.0214

Gnomad OTH

AF:

0.0893

GnomAD3 exomes

AF:

0.0540

AC:

13558

AN:

251276

Hom.:

810

AF XY:

0.0512

AC XY:

6954

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.0665

Gnomad ASJ exome

AF:

0.0302

Gnomad EAS exome

AF:

0.147

Gnomad SAS exome

AF:

0.0654

Gnomad FIN exome

AF:

0.00430

Gnomad NFE exome

AF:

0.0231

Gnomad OTH exome

AF:

0.0496

GnomAD4 exome

AF:

0.0322

AC:

47063

AN:

1461704

Hom.:

1893

Cov.:

AF XY:

0.0326

AC XY:

23670

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.0688

Gnomad4 ASJ exome

AF:

0.0329

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.0658

Gnomad4 FIN exome

AF:

0.00586

Gnomad4 NFE exome

AF:

0.0201

Gnomad4 OTH exome

AF:

0.0475

GnomAD4 genome

AF:

0.0794

AC:

12049

AN:

151808

Hom.:

896

Cov.:

AF XY:

0.0797

AC XY:

5910

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.195

Gnomad4 AMR

AF:

0.0719

Gnomad4 ASJ

AF:

0.0306

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.0700

Gnomad4 FIN

AF:

0.00538

Gnomad4 NFE

AF:

0.0214

Gnomad4 OTH

AF:

0.0903

Alfa

AF:

0.0370

Hom.:

487

Bravo

AF:

0.0900

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0205

AC:

ESP6500AA

AF:

0.190

AC:

835

ESP6500EA

AF:

0.0228

AC:

196

ExAC

AF:

0.0554

AC:

6723

Asia WGS

AF:

0.0940

AC:

327

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.088

T;.

Eigen

Benign

0.088

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.94

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.0069

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Uncertain

0.34

Sift

Benign

0.056

T;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.99

D;.

Vest4

0.16

MutPred

0.20

Gain of MoRF binding (P = 0.0054);.;

MPC

0.20

ClinPred

0.075

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.086

gMVP

0.83

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over