rs112317511

Variant names:

• chr11-117988450-A-G
• rs112317511
• NM_001558.4:c.136A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001558.4(IL10RA):​c.136A>G​(p.Thr46Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,614,068 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. T46T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0026 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (1 hom.)
• Consequence: IL10RA NM_001558.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.362
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007986456).
• BP6: Variant 11-117988450-A-G is Benign according to our data. Variant chr11-117988450-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 470620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00261 (398/152206) while in subpopulation AFR AF = 0.00867 (360/41510). AF 95% confidence interval is 0.00793. There are 5 homozygotes in GnomAd4. There are 166 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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.136A>G	p.Thr46Ala	missense	Exon 2 of 7	NP_001549.2	Q13651
	IL10RA	NR_026691.2		n.340A>G		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RA	ENST00000227752.8	TSL:1 MANE Select	c.136A>G	p.Thr46Ala	missense	Exon 2 of 7	ENSP00000227752.4	Q13651
	IL10RA	ENST00000529924.6	TSL:1	n.1714A>G		non_coding_transcript_exon	Exon 1 of 6
	IL10RA	ENST00000951964.1		c.130A>G	p.Thr44Ala	missense	Exon 2 of 7	ENSP00000622023.1

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 390 AN: 152088 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00850

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000851 AC: 214 AN: 251494 AF XY: 0.000633

Gnomad AFR exome AF: 0.00830

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00456

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.000424 AC: 620 AN: 1461862 Hom.: 1 Cov.: 32 AF XY: 0.000371 AC XY: 270 AN XY: 727242

African (AFR) AF: 0.00914 AC: 306 AN: 33476

American (AMR) AF: 0.000402 AC: 18 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00429 AC: 112 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.000102 AC: 113 AN: 1111984

Other (OTH) AF: 0.000911 AC: 55 AN: 60396

GnomAD4 genome AF: 0.00261 AC: 398 AN: 152206 Hom.: 5 Cov.: 32 AF XY: 0.00223 AC XY: 166 AN XY: 74400

African (AFR) AF: 0.00867 AC: 360 AN: 41510

American (AMR) AF: 0.000719 AC: 11 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68002

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00121 Hom.: 2

Bravo AF: 0.00283

ESP6500AA AF: 0.00818 AC: 36

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00110 AC: 133

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	Inflammatory bowel disease 28 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.1
DANN	Benign	0.68
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0080	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.36
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.74	T
Sift4G	Benign	0.83	T
Polyphen		0.0030	B
Vest4		0.24
MVP		0.64
MPC		0.21
ClinPred		0.0034	T
GERP RS		4.0
Varity_R		0.20
gMVP		0.39
Mutation Taster		=297/3	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: rs112317511; hg19: chr11-117859165;