rs200992970

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001558.4(IL10RA):c.67+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,552,560 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 9 hom. )

Consequence

IL10RA
NM_001558.4 splice_region, intron

Scores

Splicing: ADA: 0.0001365

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -0.385

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-117986542-T-C is Benign according to our data. Variant chr11-117986542-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 470622.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=1, Uncertain_significance=1}. Variant chr11-117986542-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00186 (284/152286) while in subpopulation NFE AF= 0.00297 (202/68010). AF 95% confidence interval is 0.00263. There are 1 homozygotes in gnomad4. There are 117 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
IL10RA	NM_001558.4 linkuse as main transcript	c.67+8T>C	splice_region_variant, intron_variant		ENST00000227752.8	NP_001549.2
IL10RA	XM_047426882.1 linkuse as main transcript	c.-265T>C	5_prime_UTR_variant	1/7		XP_047282838.1
IL10RA	NR_026691.2 linkuse as main transcript	n.141+8T>C	splice_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RA	ENST00000227752.8 linkuse as main transcript	c.67+8T>C		splice_region_variant, intron_variant		1	NM_001558.4	ENSP00000227752	P1

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

284

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00157

AC:

241

AN:

153026

Hom.:

AF XY:

0.00169

AC XY:

137

AN XY:

81160

show subpopulations

Gnomad AFR exome

AF:

0.000587

Gnomad AMR exome

AF:

0.000442

Gnomad ASJ exome

AF:

0.00143

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00347

Gnomad NFE exome

AF:

0.00271

Gnomad OTH exome

AF:

0.000920

GnomAD4 exome

AF:

0.00249

AC:

3483

AN:

1400274

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

1704

AN XY:

690890

show subpopulations

Gnomad4 AFR exome

AF:

0.000316

Gnomad4 AMR exome

AF:

0.000472

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.0000279

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00377

Gnomad4 NFE exome

AF:

0.00293

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00186

AC:

284

AN:

152286

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

117

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.00297

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00137

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inflammatory bowel disease 28

Uncertain:1Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Jun 28, 2017	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

IL10RA: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.6

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over