chr21-33304827-G-A

Position:

• chr21-33304827-G-A

Variant summary

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

The NM_001405850.1(IL10RB):​c.805-3358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 152,236 control chromosomes in the GnomAD database, including 594 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 0.077 (594 hom., cov: 32)
• Consequence: IL10RB NM_001405850.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10RB	NM_001405850.1	c.805-3358G>A		intron_variant			NP_001392779.1
IL10RB	NM_001405849.1	c.805-4149G>A		intron_variant			NP_001392778.1
IL10RB	NR_175973.1	n.746-4149G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000609556.3	c.805-3358G>A		intron_variant		5		ENSP00000489965.2
IL10RB	ENST00000637650.2	c.805-4149G>A		intron_variant		5		ENSP00000489716.2

Frequencies

GnomAD3 genomes AF: 0.0764 AC: 11628 AN: 152118 Hom.: 587 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.0542

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.0741

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

GnomAD4 genome AF: 0.0765 AC: 11651 AN: 152236 Hom.: 594 Cov.: 32 AF XY: 0.0752 AC XY: 5597 AN XY: 74436

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0870

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00870

Gnomad4 FIN AF: 0.0542

Gnomad4 NFE AF: 0.0605

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0620 Hom.: 452

Bravo AF: 0.0790

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8128184; hg19: chr21-34677132;