rs17860130

chr21-33233347-GA-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001289125.3(IFNAR2):c.-84+3133del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 152,194 control chromosomes in the GnomAD database, including 209 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.042 (209 hom., cov: 32)
• Consequence: IFNAR2 NM_001289125.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNAR2	NM_001289125.3	c.-84+3133del		intron_variant		ENST00000342136.9
IFNAR2-IL10RB	NM_001414505.1	c.-38+3133del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNAR2	ENST00000342136.9	c.-84+3133del		intron_variant		1	NM_001289125.3	P2

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6348 AN: 152076 Hom.: 209 Cov.: 32

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0369

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

GnomAD4 genome AF: 0.0417 AC: 6346 AN: 152194 Hom.: 209 Cov.: 32 AF XY: 0.0411 AC XY: 3054 AN XY: 74396

Gnomad4 AFR AF: 0.0925

Gnomad4 AMR AF: 0.0255

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0609

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0366

Alfa AF: 0.0337 Hom.: 21

Bravo AF: 0.0433

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs17860130; hg19: chr21-34605652;