ENST00000382264.7:c.853G>A

Variant names:

Variant summary

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

The ENST00000382264.7(IFNAR2):c.853G>A(p.Ala285Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 718,052 control chromosomes in the GnomAD database, including 48,370 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9532 hom., cov: 30)

Exomes 𝑓: 0.36 ( 38838 hom. )

Consequence

IFNAR2
ENST00000382264.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.773

Publications

31 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=4.6544243E-5).

BP6

Variant 21-33262573-G-A is Benign according to our data. Variant chr21-33262573-G-A is described in ClinVar as Benign. ClinVar VariationId is 402970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR2	NM_001289125.3 link	c.841-220G>A		intron_variant	Intron 8 of 8	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.841-220G>A		intron_variant	Intron 8 of 8	1	NM_001289125.3	ENSP00000343957.5		P48551-1
IFNAR2-IL10RB	ENST00000433395.7 link	c.710-5821G>A		intron_variant	Intron 7 of 12	5		ENSP00000388223.3		H0Y3Z8

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53109

AN:

151582

Hom.:

9511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.339

GnomAD2 exomes

AF:

0.387

AC:

54809

AN:

141474

AF XY:

0.388

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.445

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.317

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.360

AC:

203625

AN:

566350

Hom.:

38838

Cov.:

AF XY:

0.364

AC XY:

111628

AN XY:

306336

show subpopulations

African (AFR)

AF:

0.338

AC:

5399

AN:

15986

American (AMR)

AF:

0.441

AC:

15235

AN:

34542

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

6401

AN:

20166

East Asian (EAS)

AF:

0.566

AC:

18205

AN:

32158

South Asian (SAS)

AF:

0.464

AC:

29483

AN:

63548

European-Finnish (FIN)

AF:

0.353

AC:

12548

AN:

35582

Middle Eastern (MID)

AF:

0.394

AC:

1144

AN:

2906

European-Non Finnish (NFE)

AF:

0.315

AC:

104213

AN:

330558

Other (OTH)

AF:

0.356

AC:

10997

AN:

30904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

7070

14141

21211

28282

35352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.351

AC:

53174

AN:

151702

Hom.:

9532

Cov.:

AF XY:

0.359

AC XY:

26619

AN XY:

74068

show subpopulations

African (AFR)

AF:

0.335

AC:

13881

AN:

41380

American (AMR)

AF:

0.398

AC:

6062

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1095

AN:

3470

East Asian (EAS)

AF:

0.590

AC:

3031

AN:

5138

South Asian (SAS)

AF:

0.489

AC:

2349

AN:

4806

European-Finnish (FIN)

AF:

0.379

AC:

3959

AN:

10454

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.320

AC:

21749

AN:

67898

Other (OTH)

AF:

0.342

AC:

719

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1747

3495

5242

6990

8737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.248

Hom.:

897

Bravo

AF:

0.351

TwinsUK

AF:

0.310

AC:

1149

ALSPAC

AF:

0.293

AC:

1129

ExAC

AF:

0.243

AC:

22349

Asia WGS

AF:

0.532

AC:

1845

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 64% of patients studied by a panel of primary immunodeficiencies. Number of patients: 61. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.5

(source)

DANN

Benign

0.82

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.36

.;T

MetaRNN

Benign

0.000047

T;T

MetaSVM

Benign

-0.95

PhyloP100

0.77

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.025

Sift

Benign

0.71

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.60

P;P

Vest4

0.098

ClinPred

0.0023

GERP RS

0.56

Mutation Taster

=99/1

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over