21-33303657-C-G

Variant names:

• chr21-33303657-C-G
• rs2040107
• NM_001405850.1:c.805-4528C>G

Variant summary

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

The NM_001405850.1(IL10RB):​c.805-4528C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,156 control chromosomes in the GnomAD database, including 47,766 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 0.78 (47766 hom., cov: 32)
• Consequence: IL10RB NM_001405850.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• IL10-related early-onset inflammatory bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405850.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RB	NM_001405850.1		c.805-4528C>G		intron	N/A	NP_001392779.1	A0A1B0GU52
	IL10RB	NM_001405849.1		c.805-5319C>G		intron	N/A	NP_001392778.1	A0A1B0GTI5
	IL10RB	NR_175973.1		n.746-5319C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RB	ENST00000609556.3	TSL:5	c.805-4528C>G		intron	N/A	ENSP00000489965.2	A0A1B0GU52
	IL10RB	ENST00000637650.2	TSL:5	c.805-5319C>G		intron	N/A	ENSP00000489716.2	A0A1B0GTI5

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119253 AN: 152038 Hom.: 47722 Cov.: 32

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.784 AC: 119351 AN: 152156 Hom.: 47766 Cov.: 32 AF XY: 0.785 AC XY: 58388 AN XY: 74402

African (AFR) AF: 0.946 AC: 39286 AN: 41526

American (AMR) AF: 0.705 AC: 10780 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2133 AN: 3470

East Asian (EAS) AF: 0.753 AC: 3898 AN: 5178

South Asian (SAS) AF: 0.811 AC: 3910 AN: 4824

European-Finnish (FIN) AF: 0.787 AC: 8332 AN: 10584

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48530 AN: 67976

Other (OTH) AF: 0.764 AC: 1614 AN: 2112

Alfa AF: 0.748 Hom.: 5110

Bravo AF: 0.783

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.56
PhyloP100		-0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2040107; hg19: chr21-34675962;