rs2243498

Positions:

• chr21-33281361-G-A

Variant summary

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

The NM_000628.5(IL10RB):​c.498+1443G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 152,096 control chromosomes in the GnomAD database, including 18,221 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 0.48 (18221 hom., cov: 32)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.675

Genes affected

IL10RB (HGNC:5965): (interleukin 10 receptor subunit beta) The protein encoded by this gene belongs to the cytokine receptor family. It is an accessory chain essential for the active interleukin 10 receptor complex. Coexpression of this and IL10RA proteins has been shown to be required for IL10-induced signal transduction. This gene and three other interferon receptor genes, IFAR2, IFNAR1, and IFNGR2, form a class II cytokine receptor gene cluster located in a small region on chromosome 21. [provided by RefSeq, Jul 2008]

IFNAR2-IL10RB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10RB	NM_000628.5	c.498+1443G>A		intron_variant		ENST00000290200.7
IFNAR2-IL10RB	NM_001414505.1	c.1158+1443G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RB	ENST00000290200.7	c.498+1443G>A		intron_variant		1	NM_000628.5	P2

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72895 AN: 151978 Hom.: 18193 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.480 AC: 72964 AN: 152096 Hom.: 18221 Cov.: 32 AF XY: 0.475 AC XY: 35364 AN XY: 74380

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.450

Alfa AF: 0.467 Hom.: 2509

Bravo AF: 0.477

Asia WGS AF: 0.262 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
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: rs2243498; hg19: chr21-34653666;