chr21-33265726-C-T

Variant names:

• chr21-33265726-C-T
• rs999788
• ENST00000433395.7:c.710-2668C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001414505.1(IFNAR2-IL10RB):​c.710-2668C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 273,880 control chromosomes in the GnomAD database, including 8,393 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 0.21 (3900 hom., cov: 31)
  • Exomes 𝑓: 0.25 (4493 hom.)
• Consequence: IFNAR2-IL10RB NM_001414505.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR2	NM_001289125.3	c.*2226C>T		downstream_gene_variant		ENST00000342136.9	NP_001276054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNAR2-IL10RB	ENST00000433395.7	c.710-2668C>T		intron_variant	Intron 7 of 12	5		ENSP00000388223.3
IFNAR2	ENST00000342136.9	c.*2226C>T		downstream_gene_variant		1	NM_001289125.3	ENSP00000343957.5

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31574 AN: 151594 Hom.: 3897 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.246 AC: 30029 AN: 122168 Hom.: 4493 Cov.: 0 AF XY: 0.264 AC XY: 18326 AN XY: 69480

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.562

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.208 AC: 31595 AN: 151712 Hom.: 3900 Cov.: 31 AF XY: 0.218 AC XY: 16128 AN XY: 74136

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.209

Alfa AF: 0.198 Hom.: 692

Bravo AF: 0.209

Asia WGS AF: 0.442 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.67

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: rs999788; hg19: chr21-34638031; COSMIC: COSV51615456;