chr11-117986488-G-C

Position:

• chr11-117986488-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001558.4(IL10RA):​c.21G>C​(p.Val7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0078 in 1,556,200 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V7V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0055 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (50 hom.)
• Consequence: IL10RA NM_001558.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.40

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-117986488-G-C is Benign according to our data. Variant chr11-117986488-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 281990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117986488-G-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.4 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0055 (838/152330) while in subpopulation NFE AF= 0.00925 (629/68004). AF 95% confidence interval is 0.00865. There are 3 homozygotes in gnomad4. There are 383 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10RA	NM_001558.4	c.21G>C	p.Val7=	synonymous_variant	1/7	ENST00000227752.8
IL10RA	XM_047426882.1	c.-319G>C		5_prime_UTR_variant	1/7
IL10RA	NR_026691.2	n.95G>C		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RA	ENST00000227752.8	c.21G>C	p.Val7=	synonymous_variant	1/7	1	NM_001558.4	P1

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 839 AN: 152212 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00490

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00925

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00466 AC: 737 AN: 158048 Hom.: 7 AF XY: 0.00469 AC XY: 395 AN XY: 84174

Gnomad AFR exome AF: 0.00193

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.000945

Gnomad EAS exome AF: 0.0000848

Gnomad SAS exome AF: 0.000347

Gnomad FIN exome AF: 0.00404

Gnomad NFE exome AF: 0.00879

Gnomad OTH exome AF: 0.00475

GnomAD4 exome AF: 0.00805 AC: 11302 AN: 1403870 Hom.: 50 Cov.: 31 AF XY: 0.00767 AC XY: 5315 AN XY: 693046

Gnomad4 AFR exome AF: 0.00145

Gnomad4 AMR exome AF: 0.00316

Gnomad4 ASJ exome AF: 0.00107

Gnomad4 EAS exome AF: 0.0000554

Gnomad4 SAS exome AF: 0.000377

Gnomad4 FIN exome AF: 0.00408

Gnomad4 NFE exome AF: 0.00974

Gnomad4 OTH exome AF: 0.00590

GnomAD4 genome AF: 0.00550 AC: 838 AN: 152330 Hom.: 3 Cov.: 32 AF XY: 0.00514 AC XY: 383 AN XY: 74486

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.00925

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00680 Hom.: 0

Bravo AF: 0.00529

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inflammatory bowel disease 28 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 10, 2015

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

IL10RA: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.57

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: rs4252301; hg19: chr11-117857203;