Genetic Variant IFNA4:c.*30T>C (chr9-21186932-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021068.4(IFNA4):c.*30T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,612,506 control chromosomes in the GnomAD database, including 29,893 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4223 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25670 hom. )

Consequence

IFNA4
NM_021068.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.43

Publications

8 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA4	NM_021068.4 link	c.*30T>C		3_prime_UTR_variant	Exon 1 of 1	ENST00000421715.3	NP_066546.1	P05014

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA4	ENST00000421715.3 link	c.*30T>C		3_prime_UTR_variant	Exon 1 of 1	6	NM_021068.4	ENSP00000412897.1		P05014

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33823

AN:

151958

Hom.:

4212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.215

GnomAD2 exomes

AF:

0.209

AC:

52319

AN:

250788

AF XY:

0.195

show subpopulations

Gnomad AFR exome

AF:

0.302

Gnomad AMR exome

AF:

0.300

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.435

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.178

AC:

260189

AN:

1460430

Hom.:

25670

Cov.:

AF XY:

0.175

AC XY:

127198

AN XY:

726566

show subpopulations

African (AFR)

AF:

0.294

AC:

9792

AN:

33304

American (AMR)

AF:

0.293

AC:

13039

AN:

44534

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

5019

AN:

26118

East Asian (EAS)

AF:

0.422

AC:

16739

AN:

39692

South Asian (SAS)

AF:

0.114

AC:

9793

AN:

86136

European-Finnish (FIN)

AF:

0.188

AC:

10032

AN:

53418

Middle Eastern (MID)

AF:

0.140

AC:

740

AN:

5276

European-Non Finnish (NFE)

AF:

0.165

AC:

183709

AN:

1111680

Other (OTH)

AF:

0.188

AC:

11326

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

13314

26628

39941

53255

66569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6708

13416

20124

26832

33540

<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:

0.223

AC:

33886

AN:

152076

Hom.:

4223

Cov.:

AF XY:

0.223

AC XY:

16604

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.294

AC:

12191

AN:

41454

American (AMR)

AF:

0.257

AC:

3933

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

695

AN:

3468

East Asian (EAS)

AF:

0.415

AC:

2140

AN:

5158

South Asian (SAS)

AF:

0.112

AC:

542

AN:

4822

European-Finnish (FIN)

AF:

0.198

AC:

2094

AN:

10588

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.171

AC:

11652

AN:

67990

Other (OTH)

AF:

0.215

AC:

455

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1283

2566

3850

5133

6416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.202

Hom.:

664

Bravo

AF:

0.233

Asia WGS

AF:

0.258

AC:

897

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.46

(source)

DANN

Benign

0.55

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over