Genetic Variant IFI44L:p.His73Arg (chr1-78628133-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006820.4(IFI44L):c.218A>G(p.His73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,611,096 control chromosomes in the GnomAD database, including 104,737 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. H73L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.36 ( 10633 hom., cov: 32)

Exomes 𝑓: 0.35 ( 94104 hom. )

Consequence

IFI44L
NM_006820.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.78

Publications

50 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.300964E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

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
IFI44L	NM_006820.4	MANE Select	c.218A>G	p.His73Arg	missense	Exon 2 of 9	NP_006811.2
IFI44L	NM_001375646.1		c.218A>G	p.His73Arg	missense	Exon 3 of 10	NP_001362575.1
IFI44L	NM_001375647.1		c.-296-818A>G		intron	N/A	NP_001362576.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IFI44L	ENST00000370751.10	TSL:1 MANE Select	c.218A>G	p.His73Arg	missense	Exon 2 of 9	ENSP00000359787.4
IFI44L	ENST00000459784.6	TSL:3	c.-296-818A>G		intron	N/A	ENSP00000506096.1
IFI44L	ENST00000486882.5	TSL:1	n.2464A>G		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55274

AN:

151772

Hom.:

10623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.369

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.761

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.379

GnomAD2 exomes

AF:

0.384

AC:

95657

AN:

249252

AF XY:

0.384

show subpopulations

Gnomad AFR exome

AF:

0.367

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.755

Gnomad FIN exome

AF:

0.399

Gnomad NFE exome

AF:

0.327

Gnomad OTH exome

AF:

0.374

GnomAD4 exome

AF:

0.349

AC:

509913

AN:

1459206

Hom.:

94104

Cov.:

AF XY:

0.351

AC XY:

254856

AN XY:

725938

show subpopulations

African (AFR)

AF:

0.365

AC:

12185

AN:

33356

American (AMR)

AF:

0.359

AC:

15964

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.325

AC:

8467

AN:

26058

East Asian (EAS)

AF:

0.785

AC:

31043

AN:

39564

South Asian (SAS)

AF:

0.417

AC:

35815

AN:

85924

European-Finnish (FIN)

AF:

0.390

AC:

20773

AN:

53272

Middle Eastern (MID)

AF:

0.384

AC:

2210

AN:

5752

European-Non Finnish (NFE)

AF:

0.325

AC:

360833

AN:

1110480

Other (OTH)

AF:

0.375

AC:

22623

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

17391

34783

52174

69566

86957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11884

23768

35652

47536

59420

<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:

0.364

AC:

55334

AN:

151890

Hom.:

10633

Cov.:

AF XY:

0.369

AC XY:

27387

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.369

AC:

15311

AN:

41476

American (AMR)

AF:

0.337

AC:

5122

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

1125

AN:

3468

East Asian (EAS)

AF:

0.761

AC:

3929

AN:

5162

South Asian (SAS)

AF:

0.426

AC:

2051

AN:

4816

European-Finnish (FIN)

AF:

0.394

AC:

4153

AN:

10528

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22508

AN:

67904

Other (OTH)

AF:

0.382

AC:

805

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1721

3443

5164

6886

8607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.347

Hom.:

39022

Bravo

AF:

0.360

TwinsUK

AF:

0.330

AC:

1222

ALSPAC

AF:

0.325

AC:

1254

ESP6500AA

AF:

0.376

AC:

1658

ESP6500EA

AF:

0.327

AC:

2812

ExAC

AF:

0.381

AC:

46242

Asia WGS

AF:

0.567

AC:

1970

AN:

3478

EpiCase

AF:

0.337

EpiControl

AF:

0.324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0010

(source)

DANN

Benign

0.080

DEOGEN2

Benign

0.00047

Eigen

Benign

-2.7

Eigen_PC

Benign

-2.8

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.19

MetaRNN

Benign

9.3e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

PhyloP100

-4.8

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.33

REVEL

Benign

0.027

Sift

Benign

0.79

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.0080

MPC

0.013

ClinPred

0.0022

GERP RS

-6.2

PromoterAI

-0.0044

Neutral

(source)

Varity_R

0.026

gMVP

0.11

Mutation Taster

=100/0

polymorphism (auto)

(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