chr21-33233347-GA-G

Variant names:

• chr21-33233347-GA-G
• rs17860130
• NM_001289125.3:c.-84+3133delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001289125.3(IFNAR2):​c.-84+3133delA 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
• Publications: 1 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 -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 rank	MANE	Protein	UniProt
IFNAR2	NM_001289125.3	c.-84+3133delA		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+3132delA		intron_variant	Intron 1 of 8	1	NM_001289125.3	ENSP00000343957.5
IFNAR2-IL10RB	ENST00000433395.7	c.-38+3132delA		intron_variant	Intron 1 of 12	5		ENSP00000388223.3

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

African (AFR) AF: 0.0925 AC: 3840 AN: 41516

American (AMR) AF: 0.0255 AC: 389 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0609 AC: 294 AN: 4828

European-Finnish (FIN) AF: 0.0164 AC: 173 AN: 10570

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1492 AN: 68024

Other (OTH) AF: 0.0366 AC: 77 AN: 2106

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
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: rs17860130; hg19: chr21-34605652;