11-117993114-T-C

Position:

• chr11-117993114-T-C

Variant summary

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

The NM_001558.4(IL10RA):​c.368-127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 821,792 control chromosomes in the GnomAD database, including 138,644 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 0.51 (21463 hom., cov: 31)
  • Exomes 𝑓: 0.58 (117181 hom.)
• Consequence: IL10RA NM_001558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10RA	NM_001558.4	c.368-127T>C		intron_variant		ENST00000227752.8	NP_001549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8	c.368-127T>C		intron_variant		1	NM_001558.4	ENSP00000227752.4

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77910 AN: 151922 Hom.: 21459 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.551

GnomAD4 exome AF: 0.583 AC: 390677 AN: 669752 Hom.: 117181 Cov.: 9 AF XY: 0.584 AC XY: 207861 AN XY: 355958

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.657

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.909

Gnomad4 SAS exome AF: 0.613

Gnomad4 FIN exome AF: 0.497

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.582

GnomAD4 genome AF: 0.513 AC: 77930 AN: 152040 Hom.: 21463 Cov.: 31 AF XY: 0.516 AC XY: 38350 AN XY: 74290

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.921

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.547

Alfa AF: 0.568 Hom.: 20966

Bravo AF: 0.515

Asia WGS AF: 0.706 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.0
DANN	Benign	0.79

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: rs2508450; hg19: chr11-117863829;