chr21-33278486-A-G

Variant names:

• chr21-33278486-A-G
• rs2834168
• NM_000628.5:c.332-1266A>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.332-1266A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,188 control chromosomes in the GnomAD database, including 5,583 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 0.26 (5583 hom., cov: 32)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 15 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.332-1266A>G		intron_variant	Intron 3 of 6	ENST00000290200.7	NP_000619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7	c.332-1266A>G		intron_variant	Intron 3 of 6	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.992-1266A>G		intron_variant	Intron 9 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40253 AN: 152070 Hom.: 5587 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.265 AC: 40267 AN: 152188 Hom.: 5583 Cov.: 32 AF XY: 0.265 AC XY: 19750 AN XY: 74398

African (AFR) AF: 0.186 AC: 7742 AN: 41546

American (AMR) AF: 0.265 AC: 4053 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1305 AN: 3472

East Asian (EAS) AF: 0.194 AC: 1003 AN: 5180

South Asian (SAS) AF: 0.289 AC: 1395 AN: 4824

European-Finnish (FIN) AF: 0.270 AC: 2848 AN: 10566

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21040 AN: 67988

Other (OTH) AF: 0.278 AC: 587 AN: 2114

Alfa AF: 0.295 Hom.: 22541

Bravo AF: 0.259

Asia WGS AF: 0.197 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.14
DANN	Benign	0.71
PhyloP100		-1.6
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: rs2834168; hg19: chr21-34650791;