chr21-33304065-A-T

Variant names:

• chr21-33304065-A-T
• rs2834176
• NM_001405850.1:c.805-4120A>T

Variant summary

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

The NM_001405850.1(IL10RB):​c.805-4120A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,096 control chromosomes in the GnomAD database, including 11,198 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 0.38 (11198 hom., cov: 32)
• Consequence: IL10RB NM_001405850.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_001405850.1	c.805-4120A>T		intron_variant	Intron 6 of 6		NP_001392779.1
IL10RB	NM_001405849.1	c.805-4911A>T		intron_variant	Intron 6 of 6		NP_001392778.1
IL10RB	NR_175973.1	n.746-4911A>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000609556.3	c.805-4120A>T		intron_variant	Intron 6 of 6	5		ENSP00000489965.2
IL10RB	ENST00000637650.2	c.805-4911A>T		intron_variant	Intron 6 of 6	5		ENSP00000489716.2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57933 AN: 151976 Hom.: 11195 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.381 AC: 57950 AN: 152096 Hom.: 11198 Cov.: 32 AF XY: 0.380 AC XY: 28289 AN XY: 74350

African (AFR) AF: 0.315 AC: 13052 AN: 41494

American (AMR) AF: 0.419 AC: 6414 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1230 AN: 3468

East Asian (EAS) AF: 0.370 AC: 1916 AN: 5180

South Asian (SAS) AF: 0.415 AC: 2000 AN: 4824

European-Finnish (FIN) AF: 0.401 AC: 4243 AN: 10568

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27709 AN: 67950

Other (OTH) AF: 0.409 AC: 864 AN: 2114

Alfa AF: 0.387 Hom.: 1446

Bravo AF: 0.379

Asia WGS AF: 0.369 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.0
DANN	Benign	0.75
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs2834176; hg19: chr21-34676370;