21-33237200-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001289125.3(IFNAR2):c.-83-4640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,538 control chromosomes in the GnomAD database, including 6,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance,association (no stars).

• Frequency: Genomes: 𝑓 0.28 (6670 hom., cov: 29)
• Consequence: IFNAR2 NM_001289125.3 intron
• Clinical Significance: Uncertain significance; association no assertion criteria provided U:1 O:1
• Conservation: PhyloP100: 0.494

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-IL10RB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNAR2	NM_001289125.3	c.-83-4640G>A		intron_variant		ENST00000342136.9
IFNAR2-IL10RB	NM_001414505.1	c.-37-4686G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNAR2	ENST00000342136.9	c.-83-4640G>A		intron_variant		1	NM_001289125.3	P2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42295 AN: 151420 Hom.: 6665 Cov.: 29

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.268

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42326 AN: 151538 Hom.: 6670 Cov.: 29 AF XY: 0.291 AC XY: 21501 AN XY: 74006

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.271

Alfa AF: 0.292 Hom.: 6675

Bravo AF: 0.275

Asia WGS AF: 0.469 AC: 1629 AN: 3478

ClinVar

Significance: Uncertain significance; association

Submissions summary: Uncertain:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Associated with severe COVID-19 disease Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 01, 2023

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Mortality risk in patients with severe coronavirus disease (COVID-19) Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 06, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.4
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs3153; hg19: chr21-34609505;