chr11-117997923-G-A

Variant names:

• chr11-117997923-G-A
• rs4252287
• NM_001558.4:c.811-792G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001558.4(IL10RA):​c.811-792G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,118 control chromosomes in the GnomAD database, including 941 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 0.11 (941 hom., cov: 32)
• Consequence: IL10RA NM_001558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RA	NM_001558.4	c.811-792G>A		intron_variant	Intron 6 of 6	ENST00000227752.8	NP_001549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8	c.811-792G>A		intron_variant	Intron 6 of 6	1	NM_001558.4	ENSP00000227752.4

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16471 AN: 152000 Hom.: 936 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.108 AC: 16498 AN: 152118 Hom.: 941 Cov.: 32 AF XY: 0.108 AC XY: 8017 AN XY: 74346

African (AFR) AF: 0.109 AC: 4538 AN: 41486

American (AMR) AF: 0.144 AC: 2194 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3472

East Asian (EAS) AF: 0.0586 AC: 303 AN: 5172

South Asian (SAS) AF: 0.101 AC: 486 AN: 4810

European-Finnish (FIN) AF: 0.123 AC: 1302 AN: 10574

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7099 AN: 68010

Other (OTH) AF: 0.104 AC: 220 AN: 2110

Alfa AF: 0.105 Hom.: 1787

Bravo AF: 0.111

Asia WGS AF: 0.0760 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.67
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: rs4252287; hg19: chr11-117868638;