Variant 1-159015883-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001376587.1(IFI16):c.277G>A(p.Ala93Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 1,612,128 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 34 hom. )

Consequence

IFI16
NM_001376587.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.40

Variant links:

Genes affected

IFI16 (HGNC:5395): (interferon gamma inducible protein 16) This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of cytokines. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The protein localizes to the nucleoplasm and nucleoli, and interacts with p53 and retinoblastoma-1. It modulates p53 function, and inhibits cell growth in the Ras/Raf signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]

IFI16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004086435).

BP6

Variant 1-159015883-G-A is Benign according to our data. Variant chr1-159015883-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639481.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFI16	NM_001376587.1 linkuse as main transcript	c.277G>A	p.Ala93Thr	missense_variant	3/12	ENST00000295809.12	NP_001363516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFI16	ENST00000295809.12 linkuse as main transcript	c.277G>A	p.Ala93Thr	missense_variant	3/12	5	NM_001376587.1	ENSP00000295809	A2	Q16666-1

Frequencies

GnomAD3 genomes

AF:

0.00535

AC:

815

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00667

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00847

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00529

AC:

1329

AN:

251034

Hom.:

AF XY:

0.00537

AC XY:

728

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00520

Gnomad FIN exome

AF:

0.00236

Gnomad NFE exome

AF:

0.00813

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.00634

AC:

9258

AN:

1459808

Hom.:

Cov.:

AF XY:

0.00637

AC XY:

4628

AN XY:

726394

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00436

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00488

Gnomad4 FIN exome

AF:

0.00270

Gnomad4 NFE exome

AF:

0.00727

Gnomad4 OTH exome

AF:

0.00605

GnomAD4 genome

AF:

0.00534

AC:

814

AN:

152320

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

384

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00666

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00189

Gnomad4 NFE

AF:

0.00847

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00703

Hom.:

Bravo

AF:

0.00519

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00543

AC:

659

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00763

EpiControl

AF:

0.00646

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

IFI16: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.23

DANN

Benign

0.57

DEOGEN2

Benign

0.0018

T;T;.;.;T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00037

LIST_S2

Benign

0.32

T;T;.;T;T;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.0041

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

.;.;N;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

1.4

N;N;N;N;N;N;N

REVEL

Benign

0.014

Sift

Benign

1.0

T;T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T

Polyphen

0.73, 0.0

.;.;P;P;B;.;.

Vest4

0.083, 0.066, 0.080, 0.078

MVP

0.19

MPC

0.47

ClinPred

0.0039

GERP RS

-0.24

Varity_R

0.018

gMVP

0.045

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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