21-33241945-T-C

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.23T>C(p.Phe8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 1,608,462 control chromosomes in the GnomAD database, including 6,307 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 (★★).

Frequency

Genomes: 𝑓 0.092 ( 699 hom., cov: 32)

Exomes 𝑓: 0.083 ( 5608 hom. )

Consequence

IFNAR2
NM_001289125.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.30

Publications

40 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=0.001052022).

BP6

Variant 21-33241945-T-C is Benign according to our data. Variant chr21-33241945-T-C is described in ClinVar as [Benign]. Clinvar id is 7288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR2	NM_001289125.3 link	c.23T>C	p.Phe8Ser	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.23T>C	p.Phe8Ser	missense_variant	Exon 2 of 9	1	NM_001289125.3	ENSP00000343957.5		P48551-1
IFNAR2-IL10RB	ENST00000433395.7 link	c.23T>C	p.Phe8Ser	missense_variant	Exon 2 of 13	5		ENSP00000388223.3		H0Y3Z8

Frequencies

GnomAD3 genomes

AF:

0.0917

AC:

13949

AN:

152094

Hom.:

694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0805

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.0776

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.0932

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0816

Gnomad OTH

AF:

0.0841

GnomAD2 exomes

AF:

0.103

AC:

25757

AN:

249278

AF XY:

0.102

show subpopulations

Gnomad AFR exome

AF:

0.0774

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.0774

Gnomad EAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.0855

Gnomad NFE exome

AF:

0.0808

Gnomad OTH exome

AF:

0.0909

GnomAD4 exome

AF:

0.0825

AC:

120178

AN:

1456250

Hom.:

5608

Cov.:

AF XY:

0.0842

AC XY:

61009

AN XY:

724626

show subpopulations

African (AFR)

AF:

0.0794

AC:

2647

AN:

33326

American (AMR)

AF:

0.152

AC:

6737

AN:

44280

Ashkenazi Jewish (ASJ)

AF:

0.0775

AC:

2017

AN:

26024

East Asian (EAS)

AF:

0.146

AC:

5751

AN:

39458

South Asian (SAS)

AF:

0.124

AC:

10653

AN:

85632

European-Finnish (FIN)

AF:

0.0833

AC:

4433

AN:

53242

Middle Eastern (MID)

AF:

0.118

AC:

676

AN:

5748

European-Non Finnish (NFE)

AF:

0.0737

AC:

81696

AN:

1108390

Other (OTH)

AF:

0.0926

AC:

5568

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

4938

9876

14814

19752

24690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0917

AC:

13963

AN:

152212

Hom.:

699

Cov.:

AF XY:

0.0971

AC XY:

7227

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0805

AC:

3341

AN:

41528

American (AMR)

AF:

0.131

AC:

2010

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0776

AC:

269

AN:

3468

East Asian (EAS)

AF:

0.172

AC:

890

AN:

5184

South Asian (SAS)

AF:

0.133

AC:

644

AN:

4824

European-Finnish (FIN)

AF:

0.0932

AC:

987

AN:

10592

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0816

AC:

5548

AN:

68004

Other (OTH)

AF:

0.0894

AC:

189

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

646

1293

1939

2586

3232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0856

Hom.:

2197

Bravo

AF:

0.0936

TwinsUK

AF:

0.0777

AC:

288

ALSPAC

AF:

0.0664

AC:

256

ESP6500AA

AF:

0.0756

AC:

333

ESP6500EA

AF:

0.0779

AC:

670

ExAC

AF:

0.105

AC:

12794

Asia WGS

AF:

0.147

AC:

510

AN:

3478

EpiCase

AF:

0.0834

EpiControl

AF:

0.0849

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign: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

- -

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

Uncertain:1

May 06, 2022

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

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 29% of patients studied by a panel of primary immunodeficiencies. Number of patients: 28. 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

- -

Hepatitis B virus, susceptibility to

Other:1

Jun 13, 2006

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.76

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.097

.;.;T;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.40

.;T;.;T;T

MetaRNN

Benign

0.0011

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

N;N;N;N;.

PhyloP100

-1.3

PrimateAI

Benign

0.27

PROVEAN

Benign

0.68

N;N;N;N;N

REVEL

Benign

0.012

Sift

Benign

0.048

D;D;T;D;D

Sift4G

Benign

0.20

T;T;T;T;T

Polyphen

0.0010

B;B;B;B;.

Vest4

0.037

MPC

0.058

ClinPred

0.00058

GERP RS

-5.0

Varity_R

0.12

gMVP

0.37

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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21-33241945-T-C

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