Variant chr6-31616403-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001623.5(AIF1):c.256C>A(p.Leu86Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,613,010 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00083 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

AIF1
NM_001623.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029285938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AIF1	NM_001623.5 linkuse as main transcript	c.256C>A	p.Leu86Ile	missense_variant	5/6	ENST00000376059.8	NP_001614.3
AIF1	NM_001318970.2 linkuse as main transcript	c.94C>A	p.Leu32Ile	missense_variant	5/6		NP_001305899.1
AIF1	NM_032955.3 linkuse as main transcript	c.94C>A	p.Leu32Ile	missense_variant	2/3		NP_116573.1
AIF1	XM_005248870.5 linkuse as main transcript	c.454C>A	p.Leu152Ile	missense_variant	4/4		XP_005248927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIF1	ENST00000376059.8 linkuse as main transcript	c.256C>A	p.Leu86Ile	missense_variant	5/6	1	NM_001623.5	ENSP00000365227	P1	P55008-1
AIF1	ENST00000337917.11 linkuse as main transcript	c.298C>A	p.Leu100Ile	missense_variant	5/6	1		ENSP00000338776
AIF1	ENST00000376049.4 linkuse as main transcript	c.94C>A	p.Leu32Ile	missense_variant	2/3	1		ENSP00000365217		P55008-2
AIF1	ENST00000466820.1 linkuse as main transcript	n.871C>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.000822

AC:

125

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000629

AC:

155

AN:

246336

Hom.:

AF XY:

0.000566

AC XY:

AN XY:

134328

show subpopulations

Gnomad AFR exome

AF:

0.00200

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000461

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000570

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000377

AC:

550

AN:

1460806

Hom.:

Cov.:

AF XY:

0.000365

AC XY:

265

AN XY:

726718

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000533

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000299

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152204

Hom.:

Cov.:

AF XY:

0.000901

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000375

Hom.:

Bravo

AF:

0.000752

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00232

AC:

ESP6500EA

AF:

0.000185

AC:

ExAC

AF:

0.000552

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.00101

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 29, 2023

The c.292C>A (p.L98I) alteration is located in exon 3 (coding exon 1) of the AIF1 gene. This alteration results from a C to A substitution at nucleotide position 292, causing the leucine (L) at amino acid position 98 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

T;.;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.78

M_CAP

Benign

0.0081

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.0

M;.;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.092

T;T;T

Sift4G

Benign

0.083

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.39

MVP

0.48

MPC

0.69

ClinPred

0.020

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.50

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