11-117996682-T-C

Variant names:

• chr11-117996682-T-C
• rs2508454
• NM_001558.4:c.810+972T>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.810+972T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,134 control chromosomes in the GnomAD database, including 33,681 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 0.66 (33681 hom., cov: 33)
• Consequence: IL10RA NM_001558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 1 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: ClinGen, Ambry Genetics, 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 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.810+972T>C		intron	N/A	NP_001549.2	Q13651
	IL10RA	NM_001440423.1		c.363+972T>C		intron	N/A	NP_001427352.1
	IL10RA	NR_026691.2		n.1014+972T>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.810+972T>C		intron	N/A	ENSP00000227752.4	Q13651
	IL10RA	ENST00000529924.6	TSL:1	n.2388+972T>C		intron	N/A
	IL10RA	ENST00000951964.1		c.804+972T>C		intron	N/A	ENSP00000622023.1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100141 AN: 152014 Hom.: 33661 Cov.: 33

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.659 AC: 100197 AN: 152134 Hom.: 33681 Cov.: 33 AF XY: 0.660 AC XY: 49117 AN XY: 74376

African (AFR) AF: 0.550 AC: 22817 AN: 41488

American (AMR) AF: 0.760 AC: 11624 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2395 AN: 3472

East Asian (EAS) AF: 0.977 AC: 5062 AN: 5180

South Asian (SAS) AF: 0.726 AC: 3502 AN: 4826

European-Finnish (FIN) AF: 0.614 AC: 6505 AN: 10586

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46013 AN: 67966

Other (OTH) AF: 0.678 AC: 1429 AN: 2108

Alfa AF: 0.668 Hom.: 4216

Bravo AF: 0.666

Asia WGS AF: 0.788 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.20
PhyloP100		-1.2
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: rs2508454; hg19: chr11-117867397;