rs962859

Variant names:

• chr21-33275818-A-C
• rs962859
• NM_000628.5:c.174-778A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000628.5(IL10RB):​c.174-778A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,106 control chromosomes in the GnomAD database, including 10,899 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 0.37 (10899 hom., cov: 32)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 12 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.174-778A>C		intron_variant	Intron 2 of 6	ENST00000290200.7	NP_000619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7	c.174-778A>C		intron_variant	Intron 2 of 6	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.834-778A>C		intron_variant	Intron 8 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55802 AN: 151988 Hom.: 10895 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.367 AC: 55825 AN: 152106 Hom.: 10899 Cov.: 32 AF XY: 0.362 AC XY: 26919 AN XY: 74378

African (AFR) AF: 0.287 AC: 11927 AN: 41506

American (AMR) AF: 0.290 AC: 4432 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1563 AN: 3470

East Asian (EAS) AF: 0.174 AC: 900 AN: 5176

South Asian (SAS) AF: 0.330 AC: 1590 AN: 4822

European-Finnish (FIN) AF: 0.355 AC: 3761 AN: 10580

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30490 AN: 67944

Other (OTH) AF: 0.372 AC: 787 AN: 2116

Alfa AF: 0.410 Hom.: 21369

Bravo AF: 0.355

Asia WGS AF: 0.223 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		-0.64
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: rs962859; hg19: chr21-34648123;