rs8128184

Variant names:

• chr21-33304827-G-A
• rs8128184
• NM_001405850.1:c.805-3358G>A

Variant summary

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

The NM_001405850.1(IL10RB):​c.805-3358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 152,236 control chromosomes in the GnomAD database, including 594 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 0.077 (594 hom., cov: 32)
• Consequence: IL10RB NM_001405850.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• 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: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_001405850.1	c.805-3358G>A		intron_variant	Intron 6 of 6		NP_001392779.1
IL10RB	NM_001405849.1	c.805-4149G>A		intron_variant	Intron 6 of 6		NP_001392778.1
IL10RB	NR_175973.1	n.746-4149G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000609556.3	c.805-3358G>A		intron_variant	Intron 6 of 6	5		ENSP00000489965.2
IL10RB	ENST00000637650.2	c.805-4149G>A		intron_variant	Intron 6 of 6	5		ENSP00000489716.2

Frequencies

GnomAD3 genomes AF: 0.0764 AC: 11628 AN: 152118 Hom.: 587 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.0542

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.0741

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

GnomAD4 genome AF: 0.0765 AC: 11651 AN: 152236 Hom.: 594 Cov.: 32 AF XY: 0.0752 AC XY: 5597 AN XY: 74436

African (AFR) AF: 0.134 AC: 5549 AN: 41520

American (AMR) AF: 0.0559 AC: 856 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0870 AC: 302 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00870 AC: 42 AN: 4826

European-Finnish (FIN) AF: 0.0542 AC: 574 AN: 10600

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0605 AC: 4116 AN: 68010

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

Alfa AF: 0.0641 Hom.: 630

Bravo AF: 0.0790

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.31
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs8128184; hg19: chr21-34677132;