NM_001289125.3:c.710-586T>C

Variant names:

• chr21-33260011-T-C
• rs2250226
• NM_001289125.3:c.710-586T>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.710-586T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,048 control chromosomes in the GnomAD database, including 14,291 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 0.42 (14291 hom., cov: 32)
• Consequence: IFNAR2 NM_001289125.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.17
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289125.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR2	NM_001289125.3	MANE Select	c.710-586T>C		intron	N/A	NP_001276054.1
	IFNAR2-IL10RB	NM_001414505.1		c.709+7181T>C		intron	N/A	NP_001401434.1
	IFNAR2	NM_207585.3		c.710-586T>C		intron	N/A	NP_997468.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR2	ENST00000342136.9	TSL:1 MANE Select	c.710-586T>C		intron	N/A	ENSP00000343957.5
	IFNAR2-IL10RB	ENST00000433395.7	TSL:5	c.709+7181T>C		intron	N/A	ENSP00000388223.3
	IFNAR2	ENST00000382264.7	TSL:1	c.710-586T>C		intron	N/A	ENSP00000371699.3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63702 AN: 151928 Hom.: 14256 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.420 AC: 63793 AN: 152048 Hom.: 14291 Cov.: 32 AF XY: 0.427 AC XY: 31708 AN XY: 74326

African (AFR) AF: 0.563 AC: 23323 AN: 41448

American (AMR) AF: 0.436 AC: 6654 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1124 AN: 3468

East Asian (EAS) AF: 0.591 AC: 3062 AN: 5180

South Asian (SAS) AF: 0.494 AC: 2384 AN: 4828

European-Finnish (FIN) AF: 0.378 AC: 3992 AN: 10558

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.325 AC: 22083 AN: 67988

Other (OTH) AF: 0.390 AC: 825 AN: 2114

Alfa AF: 0.387 Hom.: 2498

Bravo AF: 0.432

Asia WGS AF: 0.553 AC: 1918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.37
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2250226; hg19: chr21-34632316;