Genetic Variant IFNA4:p.Ala74Pro (chr9-21187312-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021068.4(IFNA4):c.220G>C(p.Ala74Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. A74T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 30)

Failed GnomAD Quality Control

Consequence

IFNA4
NM_021068.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0350

Publications

26 publications found

Variant links:

Genes affected

IFNA4 (HGNC:5425): (interferon alpha 4) 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. [provided by Alliance of Genome Resources, Apr 2022]

IFNA4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16332528).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021068.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA4	NM_021068.4	MANE Select	c.220G>C	p.Ala74Pro	missense	Exon 1 of 1	NP_066546.1	P05014

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA4	ENST00000421715.3	TSL:6 MANE Select	c.220G>C	p.Ala74Pro	missense	Exon 1 of 1	ENSP00000412897.1	P05014

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151722

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74068

African (AFR)

AF:

0.00

AC:

AN:

41258

American (AMR)

AF:

0.00

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67956

Other (OTH)

AF:

0.00

AC:

AN:

2088

Alfa

AF:

0.00

Hom.:

10579

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.81

M_CAP

Benign

0.0042

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.3

PhyloP100

0.035

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.12

Sift

Uncertain

0.014

Sift4G

Uncertain

0.037

Polyphen

0.025

Vest4

0.35

MutPred

0.52

Gain of disorder (P = 0.0598)

MVP

0.14

MPC

1.0

ClinPred

0.49

GERP RS

1.1

PromoterAI

0.012

Neutral

(source)

Varity_R

0.74

gMVP

0.35

Mutation Taster

=98/2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over