11-117996682-T-C

Variant names:

• chr11-117996682-T-C
• rs2508454
• NM_001558.4:c.810+972T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001558.4(IL10RA):​c.810+972T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,134 control chromosomes in the GnomAD database, including 33,681 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33681 hom., cov: 33)
• Consequence: IL10RA NM_001558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RA	NM_001558.4	c.810+972T>C		intron_variant	Intron 6 of 6	ENST00000227752.8	NP_001549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8	c.810+972T>C		intron_variant	Intron 6 of 6	1	NM_001558.4	ENSP00000227752.4

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100141 AN: 152014 Hom.: 33661 Cov.: 33

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.678

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.659 AC: 100197 AN: 152134 Hom.: 33681 Cov.: 33 AF XY: 0.660 AC XY: 49117 AN XY: 74376

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.678

Alfa AF: 0.668 Hom.: 4216

Bravo AF: 0.666

Asia WGS AF: 0.788 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.20

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: rs2508454; hg19: chr11-117867397;