rs2244305

Variant names:

• chr21-33280653-C-T
• rs2244305
• NM_000628.5:c.498+735C>T

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+735C>T 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 151,948 control chromosomes in the GnomAD database, including 18,202 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 (18202 hom., cov: 32)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.498+735C>T		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+735C>T		intron_variant	Intron 4 of 6	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.1158+735C>T		intron_variant	Intron 10 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72852 AN: 151832 Hom.: 18178 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: 0.204

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.430

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: 72912 AN: 151948 Hom.: 18202 Cov.: 32 AF XY: 0.476 AC XY: 35331 AN XY: 74268

African (AFR) AF: 0.617 AC: 25541 AN: 41416

American (AMR) AF: 0.392 AC: 5982 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1829 AN: 3466

East Asian (EAS) AF: 0.203 AC: 1051 AN: 5176

South Asian (SAS) AF: 0.365 AC: 1756 AN: 4812

European-Finnish (FIN) AF: 0.478 AC: 5039 AN: 10544

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.447 AC: 30350 AN: 67946

Other (OTH) AF: 0.450 AC: 951 AN: 2114

Alfa AF: 0.458 Hom.: 44481

Bravo AF: 0.477

Asia WGS AF: 0.261 AC: 907 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	0.14
DANN	Benign	0.62
PhyloP100		-1.4
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: rs2244305; hg19: chr21-34652958;