NM_000628.5:c.647-1013A>G

Variant names:

• chr21-33287091-A-G
• rs2266590
• NM_000628.5:c.647-1013A>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.647-1013A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,940 control chromosomes in the GnomAD database, including 20,959 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 0.51 (20959 hom., cov: 30)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.647-1013A>G		intron_variant	Intron 5 of 6	ENST00000290200.7	NP_000619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7	c.647-1013A>G		intron_variant	Intron 5 of 6	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.1307-1013A>G		intron_variant	Intron 11 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77357 AN: 151822 Hom.: 20917 Cov.: 30

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.510 AC: 77441 AN: 151940 Hom.: 20959 Cov.: 30 AF XY: 0.505 AC XY: 37506 AN XY: 74276

African (AFR) AF: 0.696 AC: 28835 AN: 41420

American (AMR) AF: 0.409 AC: 6240 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1937 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1080 AN: 5172

South Asian (SAS) AF: 0.376 AC: 1810 AN: 4808

European-Finnish (FIN) AF: 0.474 AC: 5007 AN: 10556

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30910 AN: 67942

Other (OTH) AF: 0.481 AC: 1009 AN: 2098

Alfa AF: 0.475 Hom.: 3266

Bravo AF: 0.511

Asia WGS AF: 0.273 AC: 950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.25
PhyloP100		-1.2
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: rs2266590; hg19: chr21-34659396;