chr21-33260011-T-C

Position:

• chr21-33260011-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.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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNAR2	NM_001289125.3	c.710-586T>C		intron_variant		ENST00000342136.9
IFNAR2-IL10RB	NM_001414505.1	c.709+7181T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNAR2	ENST00000342136.9	c.710-586T>C		intron_variant		1	NM_001289125.3	P2

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

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.390

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2250226; hg19: chr21-34632316;