NM_001558.4:c.972C>T

Variant names:

• chr11-117998876-C-T
• rs2229115
• NM_001558.4:c.972C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001558.4(IL10RA):​c.972C>T​(p.Thr324Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,614,160 control chromosomes in the GnomAD database, including 588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T324T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.037 (245 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (343 hom.)
• Consequence: IL10RA NM_001558.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.218
• Publications: 6 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 11-117998876-C-T is Benign according to our data. Variant chr11-117998876-C-T is described in ClinVar as Benign. ClinVar VariationId is 302553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.218 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 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.972C>T	p.Thr324Thr	synonymous	Exon 7 of 7	NP_001549.2	Q13651
	IL10RA	NM_001440423.1		c.525C>T	p.Thr175Thr	synonymous	Exon 5 of 5	NP_001427352.1
	IL10RA	NR_026691.2		n.1176C>T		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	ENST00000227752.8	TSL:1 MANE Select	c.972C>T	p.Thr324Thr	synonymous	Exon 7 of 7	ENSP00000227752.4	Q13651
	IL10RA	ENST00000529924.6	TSL:1	n.2550C>T		non_coding_transcript_exon	Exon 6 of 6
	IL10RA	ENST00000951964.1		c.966C>T	p.Thr322Thr	synonymous	Exon 7 of 7	ENSP00000622023.1

Frequencies

GnomAD3 genomes AF: 0.0367 AC: 5590 AN: 152162 Hom.: 246 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00197

Gnomad OTH AF: 0.0353

GnomAD2 exomes AF: 0.0170 AC: 4274 AN: 251436 AF XY: 0.0143

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.0254

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.0190

Gnomad FIN exome AF: 0.0101

Gnomad NFE exome AF: 0.00208

Gnomad OTH exome AF: 0.0170

GnomAD4 exome AF: 0.00733 AC: 10716 AN: 1461880 Hom.: 343 Cov.: 31 AF XY: 0.00712 AC XY: 5178 AN XY: 727242

African (AFR) AF: 0.114 AC: 3802 AN: 33478

American (AMR) AF: 0.0272 AC: 1217 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 445 AN: 26136

East Asian (EAS) AF: 0.0191 AC: 760 AN: 39700

South Asian (SAS) AF: 0.0155 AC: 1338 AN: 86256

European-Finnish (FIN) AF: 0.0107 AC: 572 AN: 53414

Middle Eastern (MID) AF: 0.0269 AC: 155 AN: 5768

European-Non Finnish (NFE) AF: 0.00135 AC: 1503 AN: 1112008

Other (OTH) AF: 0.0153 AC: 924 AN: 60396

GnomAD4 genome AF: 0.0368 AC: 5601 AN: 152280 Hom.: 245 Cov.: 32 AF XY: 0.0363 AC XY: 2704 AN XY: 74470

African (AFR) AF: 0.111 AC: 4603 AN: 41540

American (AMR) AF: 0.0274 AC: 419 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.0174 AC: 90 AN: 5186

South Asian (SAS) AF: 0.0182 AC: 88 AN: 4824

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00197 AC: 134 AN: 68016

Other (OTH) AF: 0.0378 AC: 80 AN: 2116

Alfa AF: 0.0124 Hom.: 105

Bravo AF: 0.0418

Asia WGS AF: 0.0640 AC: 222 AN: 3478

EpiCase AF: 0.00196

EpiControl AF: 0.00302

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Inflammatory bowel disease 28 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.9
DANN	Benign	0.59
PhyloP100		0.22
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: rs2229115; hg19: chr11-117869591; COSMIC: COSV57139602; COSMIC: COSV57139602;