NM_001289125.3:c.28T>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001289125.3(IFNAR2):c.28T>G(p.Phe10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,606,830 control chromosomes in the GnomAD database, including 95,222 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F10I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.32 ( 8284 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86938 hom. )

Consequence

IFNAR2
NM_001289125.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -1.92

Publications

65 publications found

Variant links:

Genes affected

IFNAR2 (HGNC:5433): (interferon alpha and beta receptor subunit 2) The protein encoded by this gene is a type I membrane protein that forms one of the two chains of a receptor for interferons alpha and beta. Binding and activation of the receptor stimulates Janus protein kinases, which in turn phosphorylate several proteins, including STAT1 and STAT2. The protein belongs to the type II cytokine receptor family. Mutations in this gene are associated with Immunodeficiency 45. [provided by RefSeq, Jul 2020]

IFNAR2 Gene-Disease associations (from GenCC):

immunodeficiency 45
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

IFNAR2 links:

IFNAR2-IL10RB (HGNC:):

IFNAR2-IL10RB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.302767E-5).

BP6

Variant 21-33241950-T-G is Benign according to our data. Variant chr21-33241950-T-G is described in ClinVar as [Benign]. Clinvar id is 1170800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR2	NM_001289125.3 link	c.28T>G	p.Phe10Val	missense_variant	Exon 2 of 9	ENST00000342136.9	NP_001276054.1	P48551-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNAR2	ENST00000342136.9 link	c.28T>G	p.Phe10Val	missense_variant	Exon 2 of 9	1	NM_001289125.3	ENSP00000343957.5		P48551-1
IFNAR2-IL10RB	ENST00000433395.7 link	c.28T>G	p.Phe10Val	missense_variant	Exon 2 of 13	5		ENSP00000388223.3		H0Y3Z8

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48202

AN:

151950

Hom.:

8274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.311

GnomAD2 exomes

AF:

0.383

AC:

95264

AN:

248934

AF XY:

0.386

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.474

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.582

Gnomad FIN exome

AF:

0.391

Gnomad NFE exome

AF:

0.331

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.337

AC:

490087

AN:

1454762

Hom.:

86938

Cov.:

AF XY:

0.341

AC XY:

247021

AN XY:

723956

show subpopulations

African (AFR)

AF:

0.191

AC:

6346

AN:

33300

American (AMR)

AF:

0.467

AC:

20644

AN:

44252

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

8366

AN:

26030

East Asian (EAS)

AF:

0.565

AC:

22307

AN:

39460

South Asian (SAS)

AF:

0.470

AC:

40164

AN:

85538

European-Finnish (FIN)

AF:

0.385

AC:

20454

AN:

53190

Middle Eastern (MID)

AF:

0.396

AC:

2276

AN:

5752

European-Non Finnish (NFE)

AF:

0.315

AC:

348576

AN:

1107126

Other (OTH)

AF:

0.349

AC:

20954

AN:

60114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

14457

28914

43372

57829

72286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.317

AC:

48244

AN:

152068

Hom.:

8284

Cov.:

AF XY:

0.329

AC XY:

24420

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.198

AC:

8238

AN:

41516

American (AMR)

AF:

0.400

AC:

6106

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

1106

AN:

3472

East Asian (EAS)

AF:

0.580

AC:

3003

AN:

5180

South Asian (SAS)

AF:

0.492

AC:

2373

AN:

4824

European-Finnish (FIN)

AF:

0.404

AC:

4252

AN:

10534

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.326

AC:

22171

AN:

67954

Other (OTH)

AF:

0.315

AC:

664

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1657

3313

4970

6626

8283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.319

Hom.:

17923

Bravo

AF:

0.311

TwinsUK

AF:

0.315

AC:

1168

ALSPAC

AF:

0.299

AC:

1151

ESP6500AA

AF:

0.188

AC:

828

ESP6500EA

AF:

0.317

AC:

2726

ExAC

AF:

0.378

AC:

45947

Asia WGS

AF:

0.519

AC:

1801

AN:

3478

EpiCase

AF:

0.333

EpiControl

AF:

0.337

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 69% of patients studied by a panel of primary immunodeficiencies. Number of patients: 66. Only high quality variants are reported. -

Immunodeficiency 45

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mortality risk in patients with severe coronavirus disease (COVID-19)

Other:1

May 06, 2022

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance:association

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.0080

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.10

.;.;T;.;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.15

.;T;.;T;T

MetaRNN

Benign

0.000033

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.3

N;N;N;N;.

PhyloP100

-1.9

PrimateAI

Benign

0.26

PROVEAN

Benign

1.6

N;N;N;N;N

REVEL

Benign

0.0050

Sift

Benign

0.77

T;T;T;T;T

Sift4G

Benign

0.62

T;T;T;T;T

Polyphen

0.0

B;B;B;B;.

Vest4

0.046

MPC

0.046

ClinPred

0.0044

GERP RS

-7.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.052

gMVP

0.35

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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NM_001289125.3:c.28T>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over