Variant 1-159018529-C-T 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.850C>T(p.Pro284Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00825 in 1,613,796 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P284T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0057 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 60 hom. )

Consequence

IFI16
NM_001376587.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.79

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=0.004410118).

BP6

Variant 1-159018529-C-T is Benign according to our data. Variant chr1-159018529-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639482.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI16	NM_001376587.1 linkuse as main transcript	c.850C>T	p.Pro284Ser	missense_variant	5/12	ENST00000295809.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFI16	ENST00000295809.12 linkuse as main transcript	c.850C>T	p.Pro284Ser	missense_variant	5/12	5	NM_001376587.1	A2	Q16666-1

Frequencies

GnomAD3 genomes

AF:

0.00571

AC:

869

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00915

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00586

AC:

1474

AN:

251336

Hom.:

AF XY:

0.00595

AC XY:

808

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00428

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.00189

Gnomad NFE exome

AF:

0.00851

Gnomad OTH exome

AF:

0.00751

GnomAD4 exome

AF:

0.00851

AC:

12439

AN:

1461540

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

6122

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00449

Gnomad4 ASJ exome

AF:

0.0201

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00155

Gnomad4 FIN exome

AF:

0.00206

Gnomad4 NFE exome

AF:

0.00976

Gnomad4 OTH exome

AF:

0.00889

GnomAD4 genome

AF:

0.00570

AC:

868

AN:

152256

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

384

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00169

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00915

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00865

Hom.:

Bravo

AF:

0.00603

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0145

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00988

AC:

ExAC

AF:

0.00539

AC:

655

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00911

EpiControl

AF:

0.0104

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

Nov 01, 2022

IFI16: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

Cadd

Benign

7.1

Dann

Benign

0.95

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.018

M_CAP

Benign

0.0035

MetaRNN

Benign

0.0044

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.2

L;L;L;.;L;.

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-5.1

D;D;D;D;D;D

REVEL

Benign

0.028

Sift

Uncertain

0.023

D;D;T;T;T;T

Sift4G

Benign

0.33

T;T;T;T;T;T

Polyphen

0.091

B;B;P;.;.;.

Vest4

0.20

MVP

0.23

MPC

0.26

ClinPred

0.023

GERP RS

-2.6

Varity_R

0.11

gMVP

0.022

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