dbSNP rs10120977: IFNA2:c.*399T>C (chr9-21384364-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_000605.4(IFNA2):c.*399T>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 0.147 in 152,502 control chromosomes in the GnomAD database, including 2,067 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 0.15 ( 2067 hom., cov: 32)

Exomes 𝑓: 0.12 ( 0 hom. )

Consequence

IFNA2
NM_000605.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17

Publications

17 publications found

Variant links:

Genes affected

IFNA2 (HGNC:5423): (interferon alpha 2) This gene is a member of the alpha interferon gene cluster on chromosome 9. The encoded cytokine is a member of the type I interferon family that is produced in response to viral infection as a key part of the innate immune response with potent antiviral, antiproliferative and immunomodulatory properties. This cytokine, like other type I interferons, binds a plasma membrane receptor made of IFNAR1 and IFNAR2 that is ubiquitously expressed, and thus is able to act on virtually all body cells. The encoded protein is effective in reducing the symptoms and duration of the common cold and in treating many types of cancer, including some hematological malignancies and solid tumors. A deficiency of type I interferon in the blood is thought to be a hallmark of severe COVID-19 and may provide a rationale for a combined therapeutic approach. [provided by RefSeq, Aug 2020]

IFNA2 links:

MIR31HG (HGNC:37187): (MIR31 host gene) This gene produces a long non-coding RNA that acts as a host gene for miR-31. This transcript may be involved in cellular pluripotency and regulate the differentiation of myoblasts and other tissues. This RNA was found to interact with Polycomb repressive proteins to repression transcription of genes involves in cell senescence. [provided by RefSeq, Dec 2017]

MIR31HG links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA2	NM_000605.4 link	c.*399T>C		3_prime_UTR_variant	Exon 1 of 1	ENST00000380206.4	NP_000596.2	P01563A0A7R8GUN5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IFNA2	ENST00000380206.4 link	c.*399T>C	3_prime_UTR_variant	Exon 1 of 1	6	NM_000605.4	ENSP00000369554.2	P01563
MIR31HG	ENST00000698342.1 link	n.726-4005T>C	intron_variant	Intron 2 of 2
MIR31HG	ENST00000773559.1 link	n.372-4336T>C	intron_variant	Intron 1 of 4
MIR31HG	ENST00000773560.1 link	n.1039-4005T>C	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22363

AN:

152118

Hom.:

2067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0486

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.00211

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.165

GnomAD4 exome

AF:

0.121

AC:

AN:

264

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.142

AC:

AN:

226

Other (OTH)

AF:

0.00

AC:

AN:

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:

0.147

AC:

22359

AN:

152238

Hom.:

2067

Cov.:

AF XY:

0.146

AC XY:

10840

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0484

AC:

2014

AN:

41576

American (AMR)

AF:

0.132

AC:

2022

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

688

AN:

3472

East Asian (EAS)

AF:

0.00212

AC:

AN:

5190

South Asian (SAS)

AF:

0.182

AC:

878

AN:

4830

European-Finnish (FIN)

AF:

0.177

AC:

1873

AN:

10584

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14174

AN:

67970

Other (OTH)

AF:

0.163

AC:

344

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

967

1934

2902

3869

4836

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.201

Hom.:

3512

Bravo

AF:

0.138

Asia WGS

AF:

0.0970

AC:

336

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.65

(source)

DANN

Benign

0.72

PhyloP100

-1.2

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