chr21-33293855-A-G

Variant names:

• chr21-33293855-A-G
• rs999261
• NM_000628.5:c.805-2329A>G

Variant summary

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

The NM_000628.5(IL10RB):​c.805-2329A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,106 control chromosomes in the GnomAD database, including 2,581 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 0.16 (2581 hom., cov: 32)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 16 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 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.805-2329A>G		intron	N/A	NP_000619.3
	IFNAR2-IL10RB	NM_001414505.1		c.1465-2329A>G		intron	N/A	NP_001401434.1
	IL10RB	NM_001405850.1		c.804+5594A>G		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.805-2329A>G		intron	N/A	ENSP00000290200.2
	IFNAR2-IL10RB	ENST00000433395.7	TSL:5	c.1465-2329A>G		intron	N/A	ENSP00000388223.3
	IL10RB	ENST00000609556.3	TSL:5	c.804+5594A>G		intron	N/A	ENSP00000489965.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24540 AN: 151986 Hom.: 2581 Cov.: 32

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.161 AC: 24541 AN: 152106 Hom.: 2581 Cov.: 32 AF XY: 0.167 AC XY: 12403 AN XY: 74332

African (AFR) AF: 0.0424 AC: 1763 AN: 41554

American (AMR) AF: 0.224 AC: 3417 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 457 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1998 AN: 5174

South Asian (SAS) AF: 0.242 AC: 1167 AN: 4826

European-Finnish (FIN) AF: 0.237 AC: 2489 AN: 10500

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12668 AN: 67992

Other (OTH) AF: 0.163 AC: 344 AN: 2110

Alfa AF: 0.188 Hom.: 2159

Bravo AF: 0.159

Asia WGS AF: 0.351 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.72
PhyloP100		-0.15
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: rs999261; hg19: chr21-34666160;