Variant 1-78650629-A-T 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.434A>T(p.Asp145Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000093 in 1,591,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

IFI44
NM_006417.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

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=0.02282384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFI44	NM_006417.5 linkuse as main transcript	c.434A>T	p.Asp145Val	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.434A>T	p.Asp145Val	missense_variant	2/9	1	NM_006417.5	ENSP00000359783.4		Q8TCB0-1

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000119

AC:

AN:

226384

Hom.:

AF XY:

0.0000898

AC XY:

AN XY:

122522

show subpopulations

Gnomad AFR exome

AF:

0.00175

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000410

AC:

AN:

1438692

Hom.:

Cov.:

AF XY:

0.0000322

AC XY:

AN XY:

714474

show subpopulations

Gnomad4 AFR exome

AF:

0.00174

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:

0.00

Gnomad4 OTH exome

AF:

0.0000506

GnomAD4 genome

AF:

0.000584

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000699

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

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

Apr 07, 2022

The c.434A>T (p.D145V) alteration is located in exon 2 (coding exon 1) of the IFI44 gene. This alteration results from a A to T substitution at nucleotide position 434, causing the aspartic acid (D) at amino acid position 145 to be replaced by a valine (V). 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

Uncertain

0.50

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

-0.016

Eigen_PC

Benign

-0.086

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.90

P;.

Vest4

0.38

MVP

0.63

MPC

0.038

ClinPred

0.17

GERP RS

3.3

Varity_R

0.45

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.20

Position offset: 23

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