rs8178435

chr21-33265712-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001414505.1(IFNAR2-IL10RB):c.710-2682A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 278,620 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: IFNAR2-IL10RB NM_001414505.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590

Genes affected

IFNAR2-IL10RB (HGNC:):

IL10RB-DT (HGNC:44303): (IL10RB divergent transcript)

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNAR2-IL10RB	NM_001414505.1	c.710-2682A>G		intron_variant
IL10RB-DT	NR_038974.1	n.389T>C		non_coding_transcript_exon_variant	2/2
IFNAR2	NM_001289125.3			downstream_gene_variant		ENST00000342136.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RB-DT	ENST00000411998.3	n.425T>C		non_coding_transcript_exon_variant	2/2	2
IFNAR2	ENST00000342136.9			downstream_gene_variant		1	NM_001289125.3	P2
IFNAR2	ENST00000404220.7			downstream_gene_variant		1		A2
IFNAR2	ENST00000683941.1			downstream_gene_variant				P2

Frequencies

GnomAD3 genomes AF: 0.00219 AC: 333 AN: 152012 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00764

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000150 AC: 19 AN: 126490 Hom.: 0 Cov.: 0 AF XY: 0.000126 AC XY: 9 AN XY: 71502

Gnomad4 AFR exome AF: 0.00591

Gnomad4 AMR exome AF: 0.000620

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000319

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000819

GnomAD4 genome AF: 0.00220 AC: 334 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.00211 AC XY: 157 AN XY: 74390

Gnomad4 AFR AF: 0.00764

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00215 Hom.: 0

Bravo AF: 0.00266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.9
Dann	Benign	0.39

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: rs8178435; hg19: chr21-34638017;