rs2512144

chr11-117991583-A-Gchr11-117991583-A-T

Variant summary

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

The NM_001558.4(IL10RA):c.368-1658A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 151,984 control chromosomes in the GnomAD database, including 37,485 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 0.70 (37485 hom., cov: 31)
• Consequence: IL10RA NM_001558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10RA	NM_001558.4	c.368-1658A>G		intron_variant		ENST00000227752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RA	ENST00000227752.8	c.368-1658A>G		intron_variant		1	NM_001558.4	P1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106041 AN: 151866 Hom.: 37452 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.698 AC: 106115 AN: 151984 Hom.: 37485 Cov.: 31 AF XY: 0.700 AC XY: 51998 AN XY: 74292

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.715

Alfa AF: 0.690 Hom.: 35011

Bravo AF: 0.712

Asia WGS AF: 0.856 AC: 2974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.1
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: rs2512144; hg19: chr11-117862298;