chr11-117986352-T-C

Variant names:

• chr11-117986352-T-C
• rs7925112
• NM_001558.4:c.-116T>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.-116T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 997,590 control chromosomes in the GnomAD database, including 91 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 0.016 (56 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (35 hom.)
• Consequence: IL10RA NM_001558.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963
• Publications: 2 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: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0531 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.-116T>C		upstream_gene	N/A	NP_001549.2
	IL10RA	NR_026691.2		n.-42T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	ENST00000227752.8	TSL:1 MANE Select	c.-116T>C		upstream_gene	N/A	ENSP00000227752.4
	IL10RA	ENST00000951964.1		c.-116T>C		upstream_gene	N/A	ENSP00000622023.1
	IL10RA	ENST00000885116.1		c.-116T>C		upstream_gene	N/A	ENSP00000555175.1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2407 AN: 152060 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00317 AC: 242 AN: 76282 AF XY: 0.00224

Gnomad AFR exome AF: 0.0483

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000694

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00150 AC: 1270 AN: 845412 Hom.: 35 Cov.: 11 AF XY: 0.00131 AC XY: 565 AN XY: 430370

African (AFR) AF: 0.0533 AC: 1014 AN: 19030

American (AMR) AF: 0.00279 AC: 69 AN: 24696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17328

East Asian (EAS) AF: 0.00 AC: 0 AN: 32202

South Asian (SAS) AF: 0.000171 AC: 10 AN: 58474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33420

Middle Eastern (MID) AF: 0.00141 AC: 4 AN: 2836

European-Non Finnish (NFE) AF: 0.0000453 AC: 28 AN: 618080

Other (OTH) AF: 0.00369 AC: 145 AN: 39346

GnomAD4 genome AF: 0.0158 AC: 2405 AN: 152178 Hom.: 56 Cov.: 33 AF XY: 0.0153 AC XY: 1137 AN XY: 74402

African (AFR) AF: 0.0550 AC: 2284 AN: 41526

American (AMR) AF: 0.00549 AC: 84 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67966

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.000702 Hom.: 1

Bravo AF: 0.0179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.60
PhyloP100		0.96
PromoterAI		-0.68	Under-expression
Mutation Taster		=300/0	polymorphism

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: rs7925112; hg19: chr11-117857067;