rs140466541
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_001558.4(IL10RA):c.144C>T(p.Ile48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000297 in 1,614,182 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
IL10RA
NM_001558.4 synonymous
NM_001558.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.848
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 11-117988458-C-T is Benign according to our data. Variant chr11-117988458-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 302537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.848 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0016 (244/152326) while in subpopulation AFR AF= 0.00568 (236/41570). AF 95% confidence interval is 0.00508. There are 1 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| IL10RA | NM_001558.4 | c.144C>T | p.Ile48= | synonymous_variant | 2/7 | ENST00000227752.8 | NP_001549.2 | |
| IL10RA | XM_047426882.1 | c.84C>T | p.Ile28= | synonymous_variant | 2/7 | XP_047282838.1 | ||
| IL10RA | XM_047426884.1 | c.-125C>T | 5_prime_UTR_variant | 1/5 | XP_047282840.1 | |||
| IL10RA | NR_026691.2 | n.348C>T | non_coding_transcript_exon_variant | 3/8 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| IL10RA | ENST00000227752.8 | c.144C>T | p.Ile48= | synonymous_variant | 2/7 | 1 | NM_001558.4 | ENSP00000227752 | P1 |
Frequencies
GnomAD3 genomes 0.00162 AC: 246AN: 152208Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000402 AC: 101AN: 251494Hom.: 0 AF XY: 0.000302 AC XY: 41AN XY: 135920
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GnomAD4 exome AF: 0.000161 AC: 235AN: 1461856Hom.: 0 Cov.: 32 AF XY: 0.000146 AC XY: 106AN XY: 727238
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GnomAD4 genome 0.00160 AC: 244AN: 152326Hom.: 1 Cov.: 32 AF XY: 0.00152 AC XY: 113AN XY: 74484
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inflammatory bowel disease 28 Benign:2
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at