Genetic Variant NM_006417.5:c.584T>C (chr1-78655103-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006417.5(IFI44):c.584T>C(p.Ile195Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I195V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

IFI44
NM_006417.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.918

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031606138).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006417.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IFI44	NM_006417.5	MANE Select	c.584T>C	p.Ile195Thr	missense	Exon 4 of 9	NP_006408.3
IFI44	NR_135640.1		n.244T>C		non_coding_transcript_exon	Exon 3 of 6
IFI44	NR_135641.1		n.711T>C		non_coding_transcript_exon	Exon 4 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFI44	ENST00000370747.9	TSL:1 MANE Select	c.584T>C	p.Ile195Thr	missense	Exon 4 of 9	ENSP00000359783.4	Q8TCB0-1
IFI44	ENST00000879047.1		c.584T>C	p.Ile195Thr	missense	Exon 4 of 10	ENSP00000549106.1
IFI44	ENST00000879049.1		c.584T>C	p.Ile195Thr	missense	Exon 4 of 10	ENSP00000549108.1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000203

AC:

AN:

251334

AF XY:

0.000169

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000173

AC:

253

AN:

1461686

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

130

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.0000447

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.000318

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000190

AC:

211

AN:

1111860

Other (OTH)

AF:

0.000315

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000204

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41534

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000294

Hom.:

Bravo

AF:

0.000178

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.053

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.088

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.55

M_CAP

Benign

0.0023

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.40

PhyloP100

-0.92

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.6

REVEL

Benign

0.047

Sift

Benign

0.34

Sift4G

Benign

0.29

Polyphen

0.0080

Vest4

0.10

MVP

0.25

MPC

0.011

ClinPred

0.0090

GERP RS

0.31

Varity_R

0.033

gMVP

0.34

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over