Variant rs2236757 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001289125.3(IFNAR2):c.541-50A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,577,648 control chromosomes in the GnomAD database, including 383,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37862 hom., cov: 32)

Exomes 𝑓: 0.69 ( 345865 hom. )

Consequence

IFNAR2
NM_001289125.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: -0.0720

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 (BayesDel_noAF=-0.92).

BP6

Variant 21-33252612-A-G is Benign according to our data. Variant chr21-33252612-A-G is described in ClinVar as [Benign]. Clinvar id is 1684583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNAR2	NM_001289125.3 linkuse as main transcript	c.541-50A>G		intron_variant		ENST00000342136.9	NP_001276054.1
IFNAR2-IL10RB	NM_001414505.1 linkuse as main transcript	c.541-50A>G		intron_variant			NP_001401434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNAR2	ENST00000342136.9 linkuse as main transcript	c.541-50A>G		intron_variant		1	NM_001289125.3	ENSP00000343957	P2	P48551-1

Frequencies

GnomAD3 genomes

AF:

0.701

AC:

106528

AN:

151974

Hom.:

37836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.784

Gnomad AMI

AF:

0.771

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.729

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.562

Gnomad FIN

AF:

0.636

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.706

Gnomad OTH

AF:

0.717

GnomAD3 exomes

AF:

0.643

AC:

140987

AN:

219242

Hom.:

46455

AF XY:

0.644

AC XY:

76072

AN XY:

118120

show subpopulations

Gnomad AFR exome

AF:

0.787

Gnomad AMR exome

AF:

0.537

Gnomad ASJ exome

AF:

0.723

Gnomad EAS exome

AF:

0.419

Gnomad SAS exome

AF:

0.581

Gnomad FIN exome

AF:

0.646

Gnomad NFE exome

AF:

0.697

Gnomad OTH exome

AF:

0.673

GnomAD4 exome

AF:

0.693

AC:

988191

AN:

1425556

Hom.:

345865

Cov.:

AF XY:

0.690

AC XY:

487679

AN XY:

706452

show subpopulations

Gnomad4 AFR exome

AF:

0.791

Gnomad4 AMR exome

AF:

0.546

Gnomad4 ASJ exome

AF:

0.727

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.590

Gnomad4 FIN exome

AF:

0.655

Gnomad4 NFE exome

AF:

0.714

Gnomad4 OTH exome

AF:

0.682

GnomAD4 genome

AF:

0.701

AC:

106605

AN:

152092

Hom.:

37862

Cov.:

AF XY:

0.690

AC XY:

51311

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.784

Gnomad4 AMR

AF:

0.623

Gnomad4 ASJ

AF:

0.729

Gnomad4 EAS

AF:

0.423

Gnomad4 SAS

AF:

0.562

Gnomad4 FIN

AF:

0.636

Gnomad4 NFE

AF:

0.706

Gnomad4 OTH

AF:

0.714

Alfa

AF:

0.709

Hom.:

12186

Bravo

AF:

0.703

Asia WGS

AF:

0.527

AC:

1834

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 83% of patients studied by a panel of primary immunodeficiencies. Number of patients: 79. Only high quality variants are reported. -

Immunodeficiency 45

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

Jan 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.9

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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