Variant 19-55366071-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000641.4(IL11):c.536G>A(p.Gly179Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IL11
NM_000641.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

IL11 (HGNC:5966): (interleukin 11) The protein encoded by this gene is a member of the gp130 family of cytokines. These cytokines drive the assembly of multisubunit receptor complexes, all of which contain at least one molecule of the transmembrane signaling receptor IL6ST (gp130). This cytokine is shown to stimulate the T-cell-dependent development of immunoglobulin-producing B cells. It is also found to support the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

IL11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32135195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL11	NM_000641.4 linkuse as main transcript	c.536G>A	p.Gly179Glu	missense_variant	5/5	ENST00000264563.7	NP_000632.1	P20809-1A8K3F7
IL11	NM_001267718.2 linkuse as main transcript	c.299G>A	p.Gly100Glu	missense_variant	4/4		NP_001254647.1	P20809-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL11	ENST00000264563.7 linkuse as main transcript	c.536G>A	p.Gly179Glu	missense_variant	5/5	1	NM_000641.4	ENSP00000264563.1	P20809-1
IL11	ENST00000585513.1 linkuse as main transcript	c.536G>A	p.Gly179Glu	missense_variant	5/5	1		ENSP00000467355.1	P20809-1
IL11	ENST00000590625.5 linkuse as main transcript	c.299G>A	p.Gly100Glu	missense_variant	4/4	2		ENSP00000465705.1	P20809-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000466

AC:

AN:

214772

Hom.:

AF XY:

0.00

AC XY:

AN XY:

117126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445696

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717752

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

The c.536G>A (p.G179E) alteration is located in exon 5 (coding exon 5) of the IL11 gene. This alteration results from a G to A substitution at nucleotide position 536, causing the glycine (G) at amino acid position 179 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.037

T;.;T

Eigen

Benign

0.013

Eigen_PC

Benign

0.0079

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.77

.;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.;L

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.89

N;.;.

REVEL

Benign

0.24

Sift

Benign

1.0

T;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.40

MutPred

0.70

Gain of solvent accessibility (P = 0.0281);.;Gain of solvent accessibility (P = 0.0281);

MVP

0.77

MPC

0.57

ClinPred

0.27

GERP RS

4.6

Varity_R

0.39

gMVP

0.50

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

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