rs2243498

Variant names:

• chr21-33281361-G-A
• rs2243498
• NM_000628.5:c.498+1443G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

IL10RB Gene-Disease associations (from GenCC):

• inflammatory bowel disease 25

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• IL10-related early-onset inflammatory bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IFNAR2-IL10RB (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.498+1443G>A		intron_variant	Intron 4 of 6	ENST00000290200.7	NP_000619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7	c.498+1443G>A		intron_variant	Intron 4 of 6	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.1158+1443G>A		intron_variant	Intron 10 of 12	5		ENSP00000388223.3

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

African (AFR) AF: 0.617 AC: 25595 AN: 41486

American (AMR) AF: 0.391 AC: 5980 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1832 AN: 3470

East Asian (EAS) AF: 0.202 AC: 1044 AN: 5174

South Asian (SAS) AF: 0.365 AC: 1765 AN: 4830

European-Finnish (FIN) AF: 0.477 AC: 5042 AN: 10574

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30349 AN: 67962

Other (OTH) AF: 0.450 AC: 946 AN: 2104

Alfa AF: 0.471 Hom.: 2642

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
PhyloP100		-0.68
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: rs2243498; hg19: chr21-34653666;