rs8178556

Positions:

• chr21-33294250-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000628.5(IL10RB):​c.805-1934T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 329,250 control chromosomes in the GnomAD database, including 944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.063 (375 hom., cov: 31)
  • Exomes 𝑓: 0.070 (569 hom.)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 21-33294250-T-G is Benign according to our data. Variant chr21-33294250-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10RB	NM_000628.5	c.805-1934T>G		intron_variant		ENST00000290200.7
IFNAR2-IL10RB	NM_001414505.1	c.1465-1934T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RB	ENST00000290200.7	c.805-1934T>G		intron_variant		1	NM_000628.5	P2

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9525 AN: 152024 Hom.: 373 Cov.: 31

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0584

Gnomad OTH AF: 0.0589

GnomAD4 exome AF: 0.0696 AC: 12333 AN: 177108 Hom.: 569 AF XY: 0.0764 AC XY: 7454 AN XY: 97564

Gnomad4 AFR exome AF: 0.0777

Gnomad4 AMR exome AF: 0.0263

Gnomad4 ASJ exome AF: 0.0612

Gnomad4 EAS exome AF: 0.000861

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0742

Gnomad4 NFE exome AF: 0.0576

Gnomad4 OTH exome AF: 0.0629

GnomAD4 genome AF: 0.0626 AC: 9521 AN: 152142 Hom.: 375 Cov.: 31 AF XY: 0.0638 AC XY: 4749 AN XY: 74382

Gnomad4 AFR AF: 0.0752

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0781

Gnomad4 NFE AF: 0.0584

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0587 Hom.: 436

Bravo AF: 0.0580

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.33

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: rs8178556; hg19: chr21-34666555;