21-33271777-G-T

Variant names:

• chr21-33271777-G-T
• rs2284552
• NM_000628.5:c.173+3260G>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.173+3260G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,740 control chromosomes in the GnomAD database, including 4,417 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 0.23 (4417 hom., cov: 31)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.936
• Publications: 17 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.173+3260G>T		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.173+3260G>T		intron_variant	Intron 2 of 6	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.833+3260G>T		intron_variant	Intron 8 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34768 AN: 151624 Hom.: 4415 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.229 AC: 34782 AN: 151740 Hom.: 4417 Cov.: 31 AF XY: 0.236 AC XY: 17472 AN XY: 74134

African (AFR) AF: 0.173 AC: 7144 AN: 41326

American (AMR) AF: 0.293 AC: 4470 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3464

East Asian (EAS) AF: 0.541 AC: 2789 AN: 5158

South Asian (SAS) AF: 0.319 AC: 1532 AN: 4810

European-Finnish (FIN) AF: 0.278 AC: 2920 AN: 10498

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.211 AC: 14312 AN: 67924

Other (OTH) AF: 0.228 AC: 479 AN: 2100

Alfa AF: 0.223 Hom.: 11505

Bravo AF: 0.233

Asia WGS AF: 0.443 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.8
DANN	Benign	0.63
PhyloP100		0.94
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: rs2284552; hg19: chr21-34644082;