rs2229207

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 links:

IFNAR2-IL10RB (HGNC:):

IFNAR2-IL10RB links:

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=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/exons	MANE	UniProt
IFNAR2	NM_001289125.3 linkuse as main transcript	c.23T>C	p.Phe8Ser	missense_variant	2/9	ENST00000342136.9
IFNAR2-IL10RB	NM_001414505.1 linkuse as main transcript	c.23T>C	p.Phe8Ser	missense_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNAR2	ENST00000342136.9 linkuse as main transcript	c.23T>C	p.Phe8Ser	missense_variant	2/9	1	NM_001289125.3	P2	P48551-1

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

GnomAD3 exomes

AF:

0.103

AC:

25757

AN:

249278

Hom.:

1509

AF XY:

0.102

AC XY:

13711

AN XY:

134802

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 SAS exome

AF:

0.125

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

Gnomad4 AFR exome

AF:

0.0794

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.0775

Gnomad4 EAS exome

AF:

0.146

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.0833

Gnomad4 NFE exome

AF:

0.0737

Gnomad4 OTH exome

AF:

0.0926

GnomAD4 genome

AF:

0.0917

AC:

13963

AN:

152212

Hom.:

699

Cov.:

AF XY:

0.0971

AC XY:

7227

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0805

Gnomad4 AMR

AF:

0.131

Gnomad4 ASJ

AF:

0.0776

Gnomad4 EAS

AF:

0.172

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.0932

Gnomad4 NFE

AF:

0.0816

Gnomad4 OTH

AF:

0.0894

Alfa

AF:

0.0867

Hom.:

1120

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 06, 2022

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Hepatitis B virus, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jun 13, 2006

- -

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

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;.

MutationTaster

Benign

1.0

P;P;P;P;P;P

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

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over