11-117986488-G-C

Variant names:

• chr11-117986488-G-C
• rs4252301
• NM_001558.4:c.21G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001558.4(IL10RA):​c.21G>C​(p.Val7Val) 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:5
• Conservation: PhyloP100: 2.40
• Publications: 7 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=-0.82).
• BP6: Variant 11-117986488-G-C is Benign according to our data. Variant chr11-117986488-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 281990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.21G>C	p.Val7Val	synonymous	Exon 1 of 7	NP_001549.2	Q13651
	IL10RA	NR_026691.2		n.95G>C		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	ENST00000227752.8	TSL:1 MANE Select	c.21G>C	p.Val7Val	synonymous	Exon 1 of 7	ENSP00000227752.4	Q13651
	IL10RA	ENST00000951964.1		c.21G>C	p.Val7Val	synonymous	Exon 1 of 7	ENSP00000622023.1
	IL10RA	ENST00000885116.1		c.21G>C	p.Val7Val	synonymous	Exon 1 of 7	ENSP00000555175.1

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

GnomAD2 exomes AF: 0.00466 AC: 737 AN: 158048 AF XY: 0.00469

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 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

African (AFR) AF: 0.00145 AC: 46 AN: 31772

American (AMR) AF: 0.00316 AC: 116 AN: 36732

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 27 AN: 25236

East Asian (EAS) AF: 0.0000554 AC: 2 AN: 36088

South Asian (SAS) AF: 0.000377 AC: 30 AN: 79540

European-Finnish (FIN) AF: 0.00408 AC: 200 AN: 49046

Middle Eastern (MID) AF: 0.000369 AC: 2 AN: 5420

European-Non Finnish (NFE) AF: 0.00974 AC: 10536 AN: 1081890

Other (OTH) AF: 0.00590 AC: 343 AN: 58146

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

African (AFR) AF: 0.00185 AC: 77 AN: 41596

American (AMR) AF: 0.00490 AC: 75 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00386 AC: 41 AN: 10622

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00925 AC: 629 AN: 68004

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00680 Hom.: 0

Bravo AF: 0.00529

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		2.4
PromoterAI		-0.073	Neutral
Mutation Taster		=291/9	polymorphism

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: rs4252301; hg19: chr11-117857203;