Variant 1-159016623-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_001376587.1(IFI16):c.472G>A(p.Gly158Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 0.0000075 ( 0 hom. )

Consequence

IFI16
NM_001376587.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.299

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:

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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=0.02820021).

BP6

Variant 1-159016623-G-A is Benign according to our data. Variant chr1-159016623-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2455030.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFI16	NM_001376587.1 linkuse as main transcript	c.472G>A	p.Gly158Ser	missense_variant	4/12	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.472G>A	p.Gly158Ser	missense_variant	4/12	5	NM_001376587.1	ENSP00000295809	A2	Q16666-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Feb 07, 2023

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

0.072

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.7

DANN

Benign

0.68

DEOGEN2

Benign

0.0025

T;T;.;.;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.56

T;T;.;T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.028

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.1

.;.;N;N;N;N

MutationTaster

Benign

1.0

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

PROVEAN

Benign

0.94

N;N;N;N;N;N

REVEL

Benign

0.023

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

0.57

T;T;T;T;T;T

Polyphen

0.032, 0.0010

.;.;B;B;B;.

Vest4

0.044, 0.045, 0.021, 0.023

MutPred

0.20

Gain of phosphorylation at G158 (P = 0.0086);Gain of phosphorylation at G158 (P = 0.0086);Gain of phosphorylation at G158 (P = 0.0086);Gain of phosphorylation at G158 (P = 0.0086);Gain of phosphorylation at G158 (P = 0.0086);Gain of phosphorylation at G158 (P = 0.0086);

MVP

0.16

MPC

0.18

ClinPred

0.059

GERP RS

-0.66

Varity_R

0.11

gMVP

0.048

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