rs201857411

chr11-117993293-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_001558.4(IL10RA):c.420C>T(p.Leu140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: IL10RA NM_001558.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.47

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-117993293-C-T is Benign according to our data. Variant chr11-117993293-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 538055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117993293-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-4.47 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10RA	NM_001558.4	c.420C>T	p.Leu140=	synonymous_variant	4/7	ENST00000227752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RA	ENST00000227752.8	c.420C>T	p.Leu140=	synonymous_variant	4/7	1	NM_001558.4	P1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000203 AC: 51 AN: 251476 Hom.: 0 AF XY: 0.000213 AC XY: 29 AN XY: 135920

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000231 AC: 338 AN: 1461754 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 166 AN XY: 727194

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.000276

Gnomad4 OTH exome AF: 0.000248

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74450

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000191 Hom.: 0

Bravo AF: 0.000117

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inflammatory bowel disease 28 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Nov 15, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 22, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.050
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs201857411; hg19: chr11-117864008;