Variant 19-55366059-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000641.4(IL11):c.548T>C(p.Leu183Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 1,601,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

IL11
NM_000641.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL11	NM_000641.4 linkuse as main transcript	c.548T>C	p.Leu183Pro	missense_variant	5/5	ENST00000264563.7
IL11	NM_001267718.2 linkuse as main transcript	c.311T>C	p.Leu104Pro	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL11	ENST00000264563.7 linkuse as main transcript	c.548T>C	p.Leu183Pro	missense_variant	5/5	1	NM_000641.4	P1	P20809-1
IL11	ENST00000585513.1 linkuse as main transcript	c.548T>C	p.Leu183Pro	missense_variant	5/5	1		P1	P20809-1
IL11	ENST00000590625.5 linkuse as main transcript	c.311T>C	p.Leu104Pro	missense_variant	4/4	2			P20809-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1449370

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719846

show subpopulations

Gnomad4 AFR exome

AF:

0.0000901

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:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000250

AC:

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

Dec 14, 2022

The c.548T>C (p.L183P) alteration is located in exon 5 (coding exon 5) of the IL11 gene. This alteration results from a T to C substitution at nucleotide position 548, causing the leucine (L) at amino acid position 183 to be replaced by a proline (P). 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

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.72

M_CAP

Pathogenic

0.36

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.9

L;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.4

D;.;.

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.80

MVP

0.72

MPC

0.64

ClinPred

0.96

GERP RS

4.6

Varity_R

0.97

gMVP

0.85

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