Genetic Variant IFI44L:p.Thr119Met (chr1-78628271-C-T) – 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_006820.4(IFI44L):c.356C>T(p.Thr119Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,608,910 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T119K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

IFI44L
NM_006820.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.42

Publications

4 publications found

Variant links:

Genes affected

IFI44L (HGNC:17817): (interferon induced protein 44 like) Predicted to enable GTP binding activity. Involved in defense response to virus. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IFI44L 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=0.027322203).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006820.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFI44L	NM_006820.4	MANE Select	c.356C>T	p.Thr119Met	missense	Exon 2 of 9	NP_006811.2	Q53G44-1
IFI44L	NM_001375646.1		c.356C>T	p.Thr119Met	missense	Exon 3 of 10	NP_001362575.1	Q53G44-1
IFI44L	NM_001375647.1		c.-296-680C>T		intron	N/A	NP_001362576.1	B4E019

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFI44L	ENST00000370751.10	TSL:1 MANE Select	c.356C>T	p.Thr119Met	missense	Exon 2 of 9	ENSP00000359787.4	Q53G44-1
IFI44L	ENST00000459784.6	TSL:3	c.-296-680C>T		intron	N/A	ENSP00000506096.1	B4E019
IFI44L	ENST00000486882.5	TSL:1	n.2602C>T		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000125

AC:

AN:

248756

AF XY:

0.000126

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000231

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000194

AC:

282

AN:

1456872

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

142

AN XY:

724856

show subpopulations

African (AFR)

AF:

0.0000600

AC:

AN:

33344

American (AMR)

AF:

0.0000450

AC:

AN:

44492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39504

South Asian (SAS)

AF:

0.00

AC:

AN:

85756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.000243

AC:

269

AN:

1108476

Other (OTH)

AF:

0.000149

AC:

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.0000987

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41498

American (AMR)

AF:

0.0000655

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67956

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000148

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000989

AC:

EpiCase

AF:

0.000219

EpiControl

AF:

0.000238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.012

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0042

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.47

M_CAP

Benign

0.0018

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

-2.4

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.36

REVEL

Benign

0.021

Sift

Benign

0.10

Sift4G

Benign

0.11

Polyphen

0.17

Vest4

0.070

MVP

0.048

MPC

0.013

ClinPred

0.022

GERP RS

-7.2

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.015

gMVP

0.18

Mutation Taster

=99/1

polymorphism

(source)

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

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