rs2834160

chr21-33247808-T-C

Variant summary

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

The NM_001289125.3(IFNAR2):c.395-901T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,226 control chromosomes in the GnomAD database, including 1,954 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 0.15 (1954 hom., cov: 31)
• Consequence: IFNAR2 NM_001289125.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNAR2	NM_001289125.3	c.395-901T>C		intron_variant		ENST00000342136.9
IFNAR2-IL10RB	NM_001414505.1	c.395-901T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNAR2	ENST00000342136.9	c.395-901T>C		intron_variant		1	NM_001289125.3	P2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23203 AN: 152108 Hom.: 1953 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.152 AC: 23210 AN: 152226 Hom.: 1954 Cov.: 31 AF XY: 0.147 AC XY: 10972 AN XY: 74432

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0531

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.143

Alfa AF: 0.170 Hom.: 3545

Bravo AF: 0.154

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.3
Dann	Benign	0.42

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: rs2834160; hg19: chr21-34620113;