Genetic Variant IFNA17:p.Ile184Thr (chr9-21227623-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021268.2(IFNA17):c.551T>C(p.Ile184Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000936 in 1,602,798 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. I184M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

IFNA17
NM_021268.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.760

Publications

23 publications found

Variant links:

Genes affected

IFNA17 (HGNC:5422): (interferon alpha 17) Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including B cell activation; lymphocyte activation involved in immune response; and positive regulation of peptidyl-serine phosphorylation of STAT protein. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Implicated in Crimean-Congo hemorrhagic fever and sarcoidosis. [provided by Alliance of Genome Resources, Apr 2022]

IFNA17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05147636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA17	NM_021268.2 link	c.551T>C	p.Ile184Thr	missense_variant	Exon 1 of 1	ENST00000413767.2	NP_067091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA17	ENST00000413767.2 link	c.551T>C	p.Ile184Thr	missense_variant	Exon 1 of 1	6	NM_021268.2	ENSP00000411940.2

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000881

AC:

AN:

226892

AF XY:

0.00000812

show subpopulations

Gnomad AFR exome

AF:

0.0000683

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000627

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000758

AC:

AN:

1451054

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

722188

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

32904

American (AMR)

AF:

0.00

AC:

AN:

42944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25990

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

85804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5328

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105150

Other (OTH)

AF:

0.0000834

AC:

AN:

59954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.0000264

AC:

AN:

151744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74066

show subpopulations

African (AFR)

AF:

0.0000968

AC:

AN:

41304

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67932

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.00

Hom.:

333

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.032

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.74

M_CAP

Benign

0.0025

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.34

PhyloP100

-0.76

PrimateAI

Benign

0.44

PROVEAN

Benign

1.7

REVEL

Benign

0.027

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.033

Vest4

0.056

ClinPred

0.040

GERP RS

0.95

Varity_R

0.078

gMVP

0.035

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over