rs2300370

Variant names:

• chr21-33232252-G-A
• rs2300370
• NM_001289125.3:c.-84+2036G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-33232252-G-A
• chr21-33232252-G-C

Variant summary

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

The NM_001289125.3(IFNAR2):​c.-84+2036G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,056 control chromosomes in the GnomAD database, including 8,354 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 0.32 (8354 hom., cov: 32)
• Consequence: IFNAR2 NM_001289125.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805
• Publications: 16 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR2	NM_001289125.3	c.-84+2036G>A		intron_variant	Intron 1 of 8	ENST00000342136.9	NP_001276054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNAR2	ENST00000342136.9	c.-84+2036G>A		intron_variant	Intron 1 of 8	1	NM_001289125.3	ENSP00000343957.5
IFNAR2-IL10RB	ENST00000433395.7	c.-38+2036G>A		intron_variant	Intron 1 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48757 AN: 151938 Hom.: 8344 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.321 AC: 48802 AN: 152056 Hom.: 8354 Cov.: 32 AF XY: 0.332 AC XY: 24674 AN XY: 74314

African (AFR) AF: 0.215 AC: 8907 AN: 41476

American (AMR) AF: 0.399 AC: 6097 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1097 AN: 3464

East Asian (EAS) AF: 0.581 AC: 3001 AN: 5164

South Asian (SAS) AF: 0.492 AC: 2369 AN: 4818

European-Finnish (FIN) AF: 0.403 AC: 4260 AN: 10558

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22070 AN: 67980

Other (OTH) AF: 0.316 AC: 668 AN: 2112

Alfa AF: 0.325 Hom.: 5025

Bravo AF: 0.316

Asia WGS AF: 0.521 AC: 1808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.58
PhyloP100		-0.81
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: rs2300370; hg19: chr21-34604557;