chr21-33239015-G-T

Variant names:

• chr21-33239015-G-T
• rs17860160
• NM_001289125.3:c.-83-2825G>T

Variant summary

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

The NM_001289125.3(IFNAR2):​c.-83-2825G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,254 control chromosomes in the GnomAD database, including 1,390 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 0.12 (1390 hom., cov: 32)
• Consequence: IFNAR2 NM_001289125.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR2	NM_001289125.3	c.-83-2825G>T		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.-83-2825G>T		intron_variant	Intron 1 of 8	1	NM_001289125.3	ENSP00000343957.5
IFNAR2-IL10RB	ENST00000433395.7	c.-37-2871G>T		intron_variant	Intron 1 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17598 AN: 152136 Hom.: 1391 Cov.: 32

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0526

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.116 AC: 17596 AN: 152254 Hom.: 1390 Cov.: 32 AF XY: 0.112 AC XY: 8307 AN XY: 74442

African (AFR) AF: 0.0337 AC: 1401 AN: 41546

American (AMR) AF: 0.114 AC: 1739 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5190

South Asian (SAS) AF: 0.0528 AC: 255 AN: 4826

European-Finnish (FIN) AF: 0.104 AC: 1102 AN: 10606

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12280 AN: 68000

Other (OTH) AF: 0.120 AC: 254 AN: 2114

Alfa AF: 0.152 Hom.: 306

Bravo AF: 0.111

Asia WGS AF: 0.0230 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.48
PhyloP100		-1.0
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: rs17860160; hg19: chr21-34611320;