rs1058867

Positions:

• chr21-33297076-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000628.5(IL10RB):​c.*719G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 160,450 control chromosomes in the GnomAD database, including 24,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (23022 hom., cov: 30)
  • Exomes 𝑓: 0.59 (1613 hom.)
• Consequence: IL10RB NM_000628.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.660

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]

IFNAR2-IL10RB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-33297076-G-A is Benign according to our data. Variant chr21-33297076-G-A is described in ClinVar as [Benign]. Clinvar id is 339709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10RB	NM_000628.5	c.*719G>A		3_prime_UTR_variant	7/7	ENST00000290200.7
IFNAR2-IL10RB	NM_001414505.1	c.*719G>A		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RB	ENST00000290200.7	c.*719G>A		3_prime_UTR_variant	7/7	1	NM_000628.5	P2
IL10RB	ENST00000609556.3	c.804+8815G>A		intron_variant		5		A2
IL10RB	ENST00000637650.2	c.804+8815G>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81495 AN: 151690 Hom.: 23031 Cov.: 30

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.592 AC: 5116 AN: 8642 Hom.: 1613 Cov.: 0 AF XY: 0.588 AC XY: 2603 AN XY: 4426

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.598

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.670

Gnomad4 SAS exome AF: 0.655

Gnomad4 FIN exome AF: 0.559

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.580

GnomAD4 genome AF: 0.537 AC: 81494 AN: 151808 Hom.: 23022 Cov.: 30 AF XY: 0.542 AC XY: 40195 AN XY: 74174

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.557

Alfa AF: 0.581 Hom.: 52464

Bravo AF: 0.524

Asia WGS AF: 0.705 AC: 2451 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inflammatory bowel disease 25 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs1058867; hg19: chr21-34669381;