Variant 1-78650614-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006417.5(IFI44):c.419C>G(p.Thr140Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,074 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IFI44
NM_006417.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.10

Variant links:

Genes affected

IFI44 (HGNC:16938): (interferon induced protein 44) Predicted to be involved in immune response. Predicted to act upstream of or within response to bacterium. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IFI44 links:

IFI44 (HGNC:):

IFI44 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042506278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFI44	NM_006417.5 linkuse as main transcript	c.419C>G	p.Thr140Ser	missense_variant	2/9	ENST00000370747.9	NP_006408.3	Q8TCB0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFI44	ENST00000370747.9 linkuse as main transcript	c.419C>G	p.Thr140Ser	missense_variant	2/9	1	NM_006417.5	ENSP00000359783.4		Q8TCB0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000824

AC:

AN:

242834

Hom.:

AF XY:

0.00000761

AC XY:

AN XY:

131320

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000909

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1455074

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723648

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000286

Hom.:

Bravo

AF:

0.0000151

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

Sep 29, 2023

The c.419C>G (p.T140S) alteration is located in exon 2 (coding exon 1) of the IFI44 gene. This alteration results from a C to G substitution at nucleotide position 419, causing the threonine (T) at amino acid position 140 to be replaced by a serine (S). 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

0.099

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.033

DANN

Benign

0.43

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.22

T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

0.41

N;N

REVEL

Benign

0.029

Sift

Benign

0.70

T;T

Sift4G

Benign

0.74

T;T

Polyphen

0.0070

B;.

Vest4

0.065

MutPred

0.49

Loss of sheet (P = 0.1158);.;

MVP

0.12

MPC

0.011

ClinPred

0.038

GERP RS

-4.7

Varity_R

0.024

gMVP

0.089

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