11-117995651-G-C

Variant names:

• chr11-117995651-G-C
• rs758334771
• NM_001558.4:c.751G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001558.4(IL10RA):​c.751G>C​(p.Ala251Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL10RA NM_001558.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RA	NM_001558.4	c.751G>C	p.Ala251Pro	missense_variant	Exon 6 of 7	ENST00000227752.8	NP_001549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8	c.751G>C	p.Ala251Pro	missense_variant	Exon 6 of 7	1	NM_001558.4	ENSP00000227752.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0099	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.26
Sift	Benign	0.063	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.63
MutPred		0.55		Loss of catalytic residue at A251 (P = 0.0222);
MVP		0.62
MPC		0.82
ClinPred		0.89	D
GERP RS		5.3
Varity_R		0.62
gMVP		0.84

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: rs758334771; hg19: chr11-117866366;