rs7281762

Positions:

• chr21-33297267-G-A
• chr21-33297267-G-T
• chr21-33297267-G-C

Variant summary

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

The NM_001405850.1(IL10RB):​c.804+9006G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 151,972 control chromosomes in the GnomAD database, including 2,365 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 0.16 (2365 hom., cov: 30)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: IL10RB NM_001405850.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10RB	NM_000628.5			downstream_gene_variant		ENST00000290200.7
IFNAR2-IL10RB	NM_001414505.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RB	ENST00000609556.3	c.804+9006G>A		intron_variant		5		A2
IL10RB	ENST00000637650.2	c.804+9006G>A		intron_variant		5		A2
IL10RB	ENST00000290200.7			downstream_gene_variant		1	NM_000628.5	P2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23635 AN: 151778 Hom.: 2371 Cov.: 30

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.145 AC: 11 AN: 76 Hom.: 0 Cov.: 0 AF XY: 0.111 AC XY: 4 AN XY: 36

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.155 AC: 23619 AN: 151896 Hom.: 2365 Cov.: 30 AF XY: 0.160 AC XY: 11904 AN XY: 74208

Gnomad4 AFR AF: 0.0388

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.152

Alfa AF: 0.134 Hom.: 397

Bravo AF: 0.145

Asia WGS AF: 0.323 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7281762; hg19: chr21-34669572;