Genetic Variant NM_006820.4:c.470G>C (chr1-78628385-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_006820.4(IFI44L):c.470G>C(p.Arg157Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,388,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R157Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

IFI44L
NM_006820.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

2 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: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.806

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.470G>C	p.Arg157Pro	missense	Exon 2 of 9	NP_006811.2	Q53G44-1
IFI44L	NM_001375646.1		c.470G>C	p.Arg157Pro	missense	Exon 3 of 10	NP_001362575.1	Q53G44-1
IFI44L	NM_001375647.1		c.-296-566G>C		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.470G>C	p.Arg157Pro	missense	Exon 2 of 9	ENSP00000359787.4	Q53G44-1
IFI44L	ENST00000459784.6	TSL:3	c.-296-566G>C		intron	N/A	ENSP00000506096.1	B4E019
IFI44L	ENST00000486882.5	TSL:1	n.2716G>C		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000216

AC:

AN:

1388966

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30320

American (AMR)

AF:

0.00

AC:

AN:

34394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23572

East Asian (EAS)

AF:

0.00

AC:

AN:

39112

South Asian (SAS)

AF:

0.00

AC:

AN:

77304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4662

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1070694

Other (OTH)

AF:

0.0000174

AC:

AN:

57374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.0012

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.67

M_CAP

Benign

0.0073

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

1.4

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.29

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.61

MutPred

0.76

Loss of sheet (P = 0.0457)

MVP

0.27

MPC

0.10

ClinPred

0.99

GERP RS

2.3

PromoterAI

0.021

Neutral

(source)

Varity_R

0.83

gMVP

0.82

Mutation Taster

=89/11

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over