chr21-33280616-G-T

Variant names:

• chr21-33280616-G-T
• rs2834171
• NM_000628.5:c.498+698G>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+698G>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 151,924 control chromosomes in the GnomAD database, including 18,198 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 (18198 hom., cov: 32)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000628.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RB	NM_000628.5	MANE Select	c.498+698G>T		intron	N/A	NP_000619.3
	IFNAR2-IL10RB	NM_001414505.1		c.1158+698G>T		intron	N/A	NP_001401434.1
	IL10RB	NM_001405850.1		c.498+698G>T		intron	N/A	NP_001392779.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RB	ENST00000290200.7	TSL:1 MANE Select	c.498+698G>T		intron	N/A	ENSP00000290200.2
	IFNAR2-IL10RB	ENST00000433395.7	TSL:5	c.1158+698G>T		intron	N/A	ENSP00000388223.3
	IL10RB	ENST00000609556.3	TSL:5	c.498+698G>T		intron	N/A	ENSP00000489965.2

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72846 AN: 151806 Hom.: 18174 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.480 AC: 72906 AN: 151924 Hom.: 18198 Cov.: 32 AF XY: 0.476 AC XY: 35330 AN XY: 74248

African (AFR) AF: 0.617 AC: 25557 AN: 41416

American (AMR) AF: 0.392 AC: 5980 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1827 AN: 3464

East Asian (EAS) AF: 0.204 AC: 1052 AN: 5168

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4810

European-Finnish (FIN) AF: 0.479 AC: 5048 AN: 10546

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30325 AN: 67940

Other (OTH) AF: 0.451 AC: 947 AN: 2102

Alfa AF: 0.471 Hom.: 2603

Bravo AF: 0.477

Asia WGS AF: 0.261 AC: 906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.36
PhyloP100		1.2
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: rs2834171; hg19: chr21-34652921;