11-117993114-T-C

Variant names:

• chr11-117993114-T-C
• rs2508450
• NM_001558.4:c.368-127T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

IL10RA Gene-Disease associations (from GenCC):

• inflammatory bowel disease 28

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• IL10-related early-onset inflammatory bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001558.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	NM_001558.4	MANE Select	c.368-127T>C		intron	N/A	NP_001549.2	Q13651
	IL10RA	NM_001440423.1		c.-80-127T>C		intron	N/A	NP_001427352.1
	IL10RA	NR_026691.2		n.572-127T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	ENST00000227752.8	TSL:1 MANE Select	c.368-127T>C		intron	N/A	ENSP00000227752.4	Q13651
	IL10RA	ENST00000529924.6	TSL:1	n.1946-127T>C		intron	N/A
	IL10RA	ENST00000951964.1		c.362-127T>C		intron	N/A	ENSP00000622023.1

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

African (AFR) AF: 0.316 AC: 5571 AN: 17654

American (AMR) AF: 0.657 AC: 24856 AN: 37854

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 12119 AN: 19838

East Asian (EAS) AF: 0.909 AC: 30958 AN: 34044

South Asian (SAS) AF: 0.613 AC: 40244 AN: 65616

European-Finnish (FIN) AF: 0.497 AC: 23843 AN: 47952

Middle Eastern (MID) AF: 0.573 AC: 2401 AN: 4188

European-Non Finnish (NFE) AF: 0.565 AC: 230932 AN: 408660

Other (OTH) AF: 0.582 AC: 19753 AN: 33946

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

African (AFR) AF: 0.320 AC: 13272 AN: 41468

American (AMR) AF: 0.603 AC: 9211 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2150 AN: 3472

East Asian (EAS) AF: 0.921 AC: 4766 AN: 5176

South Asian (SAS) AF: 0.622 AC: 2995 AN: 4816

European-Finnish (FIN) AF: 0.487 AC: 5145 AN: 10558

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38498 AN: 67954

Other (OTH) AF: 0.547 AC: 1155 AN: 2112

Alfa AF: 0.557 Hom.: 29489

Bravo AF: 0.515

Asia WGS AF: 0.706 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.0
DANN	Benign	0.79
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2508450; hg19: chr11-117863829;