rs2284550

Variant names:

• chr21-33245980-G-A
• rs2284550
• NM_001289125.3:c.222-738G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001289125.3(IFNAR2):​c.222-738G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,856 control chromosomes in the GnomAD database, including 17,394 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (17394 hom., cov: 31)
• Consequence: IFNAR2 NM_001289125.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• Publications: 25 publications found

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-IL10RB (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR2	NM_001289125.3	c.222-738G>A		intron_variant	Intron 4 of 8	ENST00000342136.9	NP_001276054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNAR2	ENST00000342136.9	c.222-738G>A		intron_variant	Intron 4 of 8	1	NM_001289125.3	ENSP00000343957.5
IFNAR2-IL10RB	ENST00000433395.7	c.222-738G>A		intron_variant	Intron 4 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72506 AN: 151738 Hom.: 17383 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.478 AC: 72544 AN: 151856 Hom.: 17394 Cov.: 31 AF XY: 0.473 AC XY: 35118 AN XY: 74224

African (AFR) AF: 0.458 AC: 18949 AN: 41376

American (AMR) AF: 0.457 AC: 6969 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1909 AN: 3468

East Asian (EAS) AF: 0.417 AC: 2153 AN: 5162

South Asian (SAS) AF: 0.453 AC: 2177 AN: 4810

European-Finnish (FIN) AF: 0.491 AC: 5171 AN: 10540

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33418 AN: 67926

Other (OTH) AF: 0.500 AC: 1054 AN: 2110

Alfa AF: 0.491 Hom.: 60719

Bravo AF: 0.475

Asia WGS AF: 0.434 AC: 1512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2284550; hg19: chr21-34618285;