chr21-33299436-T-C

Position:

• chr21-33299436-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001405850.1(IL10RB):​c.805-8749T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,984 control chromosomes in the GnomAD database, including 3,868 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 0.22 (3868 hom., cov: 32)
• Consequence: IL10RB NM_001405850.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10RB	NM_001405849.1	c.805-9540T>C		intron_variant
IL10RB	NM_001405850.1	c.805-8749T>C		intron_variant
IL10RB	NR_175973.1	n.746-9540T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RB	ENST00000609556.3	c.805-8749T>C		intron_variant		5		A2
IL10RB	ENST00000637650.2	c.805-9540T>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33622 AN: 151866 Hom.: 3864 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.221 AC: 33646 AN: 151984 Hom.: 3868 Cov.: 32 AF XY: 0.223 AC XY: 16551 AN XY: 74260

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.199

Alfa AF: 0.211 Hom.: 418

Bravo AF: 0.221

Asia WGS AF: 0.353 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6517158; hg19: chr21-34671741;