dbSNP rs774749917: IL11RA:p.Gln28Lys (chr9-34655299-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142784.3(IL11RA):c.82C>A(p.Gln28Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IL11RA
NM_001142784.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

Variant links:

Genes affected

IL11RA (HGNC:5967): (interleukin 11 receptor subunit alpha) Interleukin 11 is a stromal cell-derived cytokine that belongs to a family of pleiotropic and redundant cytokines that use the gp130 transducing subunit in their high affinity receptors. This gene encodes the IL-11 receptor, which is a member of the hematopoietic cytokine receptor family. This particular receptor is very similar to ciliary neurotrophic factor, since both contain an extracellular region with a 2-domain structure composed of an immunoglobulin-like domain and a cytokine receptor-like domain. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

IL11RA links:

ENSG00000258728 (HGNC:):

ENSG00000258728 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11562368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL11RA	NM_001142784.3 link	c.82C>A	p.Gln28Lys	missense_variant	Exon 2 of 13	ENST00000441545.7	NP_001136256.1	Q14626-1Q5VZ79
IL11RA	NR_052010.2 link	n.169C>A		non_coding_transcript_exon_variant	Exon 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL11RA	ENST00000441545.7 link	c.82C>A	p.Gln28Lys	missense_variant	Exon 2 of 13	5	NM_001142784.3	ENSP00000394391.3		Q14626-1
ENSG00000258728	ENST00000556278.1 link	c.514C>A	p.Gln172Lys	missense_variant	Exon 5 of 8	5		ENSP00000451792.1		G3V4G9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1453850

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.15

.;T;T;.;.;T;.;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.053

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.80

T;.;.;T;T;T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.12

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

.;M;M;.;.;M;.;.;M

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.37

N;N;N;N;N;N;N;N;.

REVEL

Benign

0.012

Sift

Benign

0.28

T;T;T;T;T;T;T;T;.

Sift4G

Uncertain

0.010

D;D;D;T;T;D;D;D;D

Polyphen

0.21

.;B;B;.;.;B;.;.;.

Vest4

0.25, 0.24, 0.25, 0.26

MutPred

0.33

.;Gain of methylation at Q28 (P = 0.0024);Gain of methylation at Q28 (P = 0.0024);Gain of methylation at Q28 (P = 0.0024);Gain of methylation at Q28 (P = 0.0024);Gain of methylation at Q28 (P = 0.0024);Gain of methylation at Q28 (P = 0.0024);Gain of methylation at Q28 (P = 0.0024);Gain of methylation at Q28 (P = 0.0024);

MVP

0.21

MPC

0.40

ClinPred

0.26

GERP RS

3.3

Varity_R

0.25

gMVP

0.36

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over