9-21187312-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021068.4(IFNA4):​c.220G>A​(p.Ala74Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,612,590 control chromosomes in the GnomAD database, including 280,134 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A74V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.59 ( 27043 hom., cov: 30)
Exomes 𝑓: 0.58 ( 253091 hom. )

Consequence

IFNA4
NM_021068.4 missense

Scores

1
17

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0350
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=1.0726089E-6).
BP6
Variant 9-21187312-C-T is Benign according to our data. Variant chr9-21187312-C-T is described in ClinVar as [Benign]. Clinvar id is 1230680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IFNA4NM_021068.4 linkc.220G>A p.Ala74Thr missense_variant Exon 1 of 1 ENST00000421715.3 NP_066546.1 P05014

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IFNA4ENST00000421715.3 linkc.220G>A p.Ala74Thr missense_variant Exon 1 of 1 6 NM_021068.4 ENSP00000412897.1 P05014

Frequencies

GnomAD3 genomes
AF:
0.594
AC:
90083
AN:
151636
Hom.:
27007
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.604
Gnomad AMI
AF:
0.602
Gnomad AMR
AF:
0.623
Gnomad ASJ
AF:
0.558
Gnomad EAS
AF:
0.849
Gnomad SAS
AF:
0.704
Gnomad FIN
AF:
0.547
Gnomad MID
AF:
0.563
Gnomad NFE
AF:
0.563
Gnomad OTH
AF:
0.604
GnomAD3 exomes
AF:
0.616
AC:
154671
AN:
250914
Hom.:
48831
AF XY:
0.614
AC XY:
83225
AN XY:
135632
show subpopulations
Gnomad AFR exome
AF:
0.609
Gnomad AMR exome
AF:
0.683
Gnomad ASJ exome
AF:
0.539
Gnomad EAS exome
AF:
0.861
Gnomad SAS exome
AF:
0.688
Gnomad FIN exome
AF:
0.550
Gnomad NFE exome
AF:
0.559
Gnomad OTH exome
AF:
0.599
GnomAD4 exome
AF:
0.585
AC:
854233
AN:
1460836
Hom.:
253091
Cov.:
76
AF XY:
0.587
AC XY:
426323
AN XY:
726692
show subpopulations
Gnomad4 AFR exome
AF:
0.603
Gnomad4 AMR exome
AF:
0.677
Gnomad4 ASJ exome
AF:
0.544
Gnomad4 EAS exome
AF:
0.862
Gnomad4 SAS exome
AF:
0.687
Gnomad4 FIN exome
AF:
0.554
Gnomad4 NFE exome
AF:
0.565
Gnomad4 OTH exome
AF:
0.592
GnomAD4 genome
AF:
0.594
AC:
90173
AN:
151754
Hom.:
27043
Cov.:
30
AF XY:
0.597
AC XY:
44257
AN XY:
74144
show subpopulations
Gnomad4 AFR
AF:
0.604
Gnomad4 AMR
AF:
0.622
Gnomad4 ASJ
AF:
0.558
Gnomad4 EAS
AF:
0.850
Gnomad4 SAS
AF:
0.705
Gnomad4 FIN
AF:
0.547
Gnomad4 NFE
AF:
0.563
Gnomad4 OTH
AF:
0.609
Alfa
AF:
0.570
Hom.:
10579
Bravo
AF:
0.601
TwinsUK
AF:
0.555
AC:
2059
ALSPAC
AF:
0.567
AC:
2185
ExAC
AF:
0.610
AC:
74075
Asia WGS
AF:
0.777
AC:
2701
AN:
3478
EpiCase
AF:
0.567
EpiControl
AF:
0.562

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Apr 26, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.74
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
6.0
DANN
Benign
0.84
DEOGEN2
Benign
0.016
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.024
N
LIST_S2
Benign
0.64
T
MetaRNN
Benign
0.0000011
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-2.5
D
REVEL
Benign
0.026
Sift
Benign
0.091
T
Sift4G
Benign
0.46
T
Polyphen
0.0010
B
Vest4
0.0030
MPC
0.61
ClinPred
0.0060
T
GERP RS
1.1
Varity_R
0.12
gMVP
0.062

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1062571; hg19: chr9-21187311; COSMIC: COSV70179653; COSMIC: COSV70179653; API