dbSNP rs779556259: IFI44L:p.Arg157Gln (chr1-78628385-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006820.4(IFI44L):c.470G>A(p.Arg157Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000506 in 1,540,968 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 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

IFI44L
NM_006820.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34395343).

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>A	p.Arg157Gln	missense	Exon 2 of 9	NP_006811.2	Q53G44-1
IFI44L	NM_001375646.1		c.470G>A	p.Arg157Gln	missense	Exon 3 of 10	NP_001362575.1	Q53G44-1
IFI44L	NM_001375647.1		c.-296-566G>A		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>A	p.Arg157Gln	missense	Exon 2 of 9	ENSP00000359787.4	Q53G44-1
IFI44L	ENST00000459784.6	TSL:3	c.-296-566G>A		intron	N/A	ENSP00000506096.1	B4E019
IFI44L	ENST00000486882.5	TSL:1	n.2716G>A		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000519

AC:

AN:

211970

AF XY:

0.0000605

show subpopulations

Gnomad AFR exome

AF:

0.0000693

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000889

Gnomad OTH exome

AF:

0.000204

GnomAD4 exome

AF:

0.0000518

AC:

AN:

1388964

Hom.:

Cov.:

AF XY:

0.0000493

AC XY:

AN XY:

690132

show subpopulations

African (AFR)

AF:

0.0000660

AC:

AN:

30320

American (AMR)

AF:

0.00

AC:

AN:

34394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23572

East Asian (EAS)

AF:

0.0000256

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:

0.0000626

AC:

AN:

1070692

Other (OTH)

AF:

0.0000349

AC:

AN:

57374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

0.0000395

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41400

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.0000315

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000248

AC:

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

0.18

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.031

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.079

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.76

M_CAP

Benign

0.0090

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

1.4

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.21

Sift

Benign

0.035

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.41

MutPred

0.72

Gain of sheet (P = 0.0827)

MVP

0.21

MPC

0.098

ClinPred

0.36

GERP RS

2.3

PromoterAI

0.0062

Neutral

(source)

Varity_R

0.25

gMVP

0.45

Mutation Taster

=86/14

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over