rs4252279

Positions:

• chr11-117996472-C-T

Variant summary

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

The NM_001558.4(IL10RA):​c.810+762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,300 control chromosomes in the GnomAD database, including 871 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 0.10 (871 hom., cov: 33)
• Consequence: IL10RA NM_001558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

Genes affected

IL10RA (HGNC:5964): (interleukin 10 receptor subunit alpha) The protein encoded by this gene is a receptor for interleukin 10. This protein is structurally related to interferon receptors. It has been shown to mediate the immunosuppressive signal of interleukin 10, and thus inhibits the synthesis of proinflammatory cytokines. This receptor is reported to promote survival of progenitor myeloid cells through the insulin receptor substrate-2/PI 3-kinase/AKT pathway. Activation of this receptor leads to tyrosine phosphorylation of JAK1 and TYK2 kinases. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10RA	NM_001558.4	c.810+762C>T		intron_variant		ENST00000227752.8	NP_001549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8	c.810+762C>T		intron_variant		1	NM_001558.4	ENSP00000227752	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15747 AN: 152182 Hom.: 866 Cov.: 33

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.0560

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0929

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

GnomAD4 genome AF: 0.104 AC: 15775 AN: 152300 Hom.: 871 Cov.: 33 AF XY: 0.103 AC XY: 7692 AN XY: 74474

Gnomad4 AFR AF: 0.0921

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.0555

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0972

Alfa AF: 0.106 Hom.: 174

Bravo AF: 0.105

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.7
DANN	Benign	0.80

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: rs4252279; hg19: chr11-117867187;