21-33299436-T-C

Variant names:

• chr21-33299436-T-C
• rs6517158
• NM_001405850.1:c.805-8749T>C

Variant summary

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

The NM_001405850.1(IL10RB):​c.805-8749T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,984 control chromosomes in the GnomAD database, including 3,868 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 0.22 (3868 hom., cov: 32)
• Consequence: IL10RB NM_001405850.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 3 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

ENSG00000294417 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RB	NM_001405850.1		c.805-8749T>C		intron	N/A	NP_001392779.1
	IL10RB	NM_001405849.1		c.805-9540T>C		intron	N/A	NP_001392778.1
	IL10RB	NR_175973.1		n.746-9540T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RB	ENST00000609556.3	TSL:5	c.805-8749T>C		intron	N/A	ENSP00000489965.2
	IL10RB	ENST00000637650.2	TSL:5	c.805-9540T>C		intron	N/A	ENSP00000489716.2
	ENSG00000294417	ENST00000723465.1		n.301-489A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33622 AN: 151866 Hom.: 3864 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.221 AC: 33646 AN: 151984 Hom.: 3868 Cov.: 32 AF XY: 0.223 AC XY: 16551 AN XY: 74260

African (AFR) AF: 0.271 AC: 11232 AN: 41414

American (AMR) AF: 0.185 AC: 2826 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1987 AN: 5166

South Asian (SAS) AF: 0.239 AC: 1153 AN: 4820

European-Finnish (FIN) AF: 0.252 AC: 2662 AN: 10582

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12703 AN: 67954

Other (OTH) AF: 0.199 AC: 420 AN: 2106

Alfa AF: 0.213 Hom.: 442

Bravo AF: 0.221

Asia WGS AF: 0.353 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.68
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs6517158; hg19: chr21-34671741;