Genetic Variant IFNAR2:c.98-43T>C (chr21-33244908-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001289125.3(IFNAR2):c.98-43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 1,601,928 control chromosomes in the GnomAD database, including 357,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.68 ( 36081 hom., cov: 31)

Exomes 𝑓: 0.66 ( 321787 hom. )

Consequence

IFNAR2
NM_001289125.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.424

Publications

37 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 21-33244908-T-C is Benign according to our data. Variant chr21-33244908-T-C is described in ClinVar as Benign. ClinVar VariationId is 1684582.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR2	NM_001289125.3 link	c.98-43T>C		intron_variant	Intron 3 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.98-43T>C		intron_variant	Intron 3 of 8	1	NM_001289125.3	ENSP00000343957.5		P48551-1
IFNAR2-IL10RB	ENST00000433395.7 link	c.98-43T>C		intron_variant	Intron 3 of 12	5		ENSP00000388223.3		H0Y3Z8

Frequencies

GnomAD3 genomes

AF:

0.683

AC:

103748

AN:

151942

Hom.:

36054

Cov.:

show subpopulations

Gnomad AFR

AF:

0.803

Gnomad AMI

AF:

0.754

Gnomad AMR

AF:

0.601

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.508

Gnomad FIN

AF:

0.595

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.673

Gnomad OTH

AF:

0.689

GnomAD2 exomes

AF:

0.615

AC:

153880

AN:

250126

AF XY:

0.612

show subpopulations

Gnomad AFR exome

AF:

0.809

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.677

Gnomad EAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.609

Gnomad NFE exome

AF:

0.667

Gnomad OTH exome

AF:

0.643

GnomAD4 exome

AF:

0.662

AC:

959695

AN:

1449868

Hom.:

321787

Cov.:

AF XY:

0.658

AC XY:

474799

AN XY:

721898

show subpopulations

African (AFR)

AF:

0.808

AC:

26840

AN:

33208

American (AMR)

AF:

0.532

AC:

23743

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.678

AC:

17615

AN:

25992

East Asian (EAS)

AF:

0.434

AC:

17163

AN:

39556

South Asian (SAS)

AF:

0.529

AC:

45445

AN:

85844

European-Finnish (FIN)

AF:

0.615

AC:

32571

AN:

52982

Middle Eastern (MID)

AF:

0.604

AC:

3473

AN:

5748

European-Non Finnish (NFE)

AF:

0.684

AC:

753824

AN:

1101950

Other (OTH)

AF:

0.651

AC:

39021

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

13913

27826

41738

55651

69564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19170

38340

57510

76680

95850

<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:

0.683

AC:

103824

AN:

152060

Hom.:

36081

Cov.:

AF XY:

0.671

AC XY:

49877

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.803

AC:

33280

AN:

41464

American (AMR)

AF:

0.601

AC:

9187

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.681

AC:

2362

AN:

3468

East Asian (EAS)

AF:

0.420

AC:

2168

AN:

5164

South Asian (SAS)

AF:

0.507

AC:

2442

AN:

4814

European-Finnish (FIN)

AF:

0.595

AC:

6284

AN:

10560

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.673

AC:

45781

AN:

67982

Other (OTH)

AF:

0.686

AC:

1447

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1614

3228

4843

6457

8071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.671

Hom.:

66261

Bravo

AF:

0.690

Asia WGS

AF:

0.481

AC:

1676

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

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

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

(source)

DANN

Benign

0.78

PhyloP100

-0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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