chr21-33266485-G-C

Variant names:

• chr21-33266485-G-C
• rs1042356155
• NM_000628.5:c.20G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000628.5(IL10RB):​c.20G>C​(p.Ser7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000647 in 1,390,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: IL10RB NM_000628.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680

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:):

IL10RB-DT (HGNC:44303): (IL10RB divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1928002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.20G>C	p.Ser7Thr	missense_variant	Exon 1 of 7	ENST00000290200.7	NP_000619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7	c.20G>C	p.Ser7Thr	missense_variant	Exon 1 of 7	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.710-1909G>C		intron_variant	Intron 7 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000647 AC: 9 AN: 1390382 Hom.: 0 Cov.: 31 AF XY: 0.00000437 AC XY: 3 AN XY: 686270

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000741

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.72
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PROVEAN	Benign	0.040	N
REVEL	Benign	0.056
Sift	Benign	0.72	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.60		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.40
MPC		0.29
ClinPred		0.058	T
GERP RS		-0.92
Varity_R		0.046
gMVP		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: rs1042356155; hg19: chr21-34638790;