Variant 19-55368227-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000641.4(IL11):c.412C>T(p.Arg138Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,533,952 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R138H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000096 ( 1 hom. )

Consequence

IL11
NM_000641.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05167696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL11	NM_000641.4 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	4/5	ENST00000264563.7
IL11	NM_001267718.2 linkuse as main transcript	c.175C>T	p.Arg59Cys	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL11	ENST00000264563.7 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	4/5	1	NM_000641.4	P1	P20809-1
IL11	ENST00000585513.1 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	4/5	1		P1	P20809-1
IL11	ENST00000590625.5 linkuse as main transcript	c.175C>T	p.Arg59Cys	missense_variant	3/4	2			P20809-2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000207

AC:

AN:

144938

Hom.:

AF XY:

0.000154

AC XY:

AN XY:

78072

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000409

Gnomad ASJ exome

AF:

0.000122

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000177

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.0000922

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000962

AC:

133

AN:

1381924

Hom.:

Cov.:

AF XY:

0.0000899

AC XY:

AN XY:

678592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000565

Gnomad4 ASJ exome

AF:

0.0000400

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000190

Gnomad4 FIN exome

AF:

0.00129

Gnomad4 NFE exome

AF:

0.0000431

Gnomad4 OTH exome

AF:

0.0000876

GnomAD4 genome

AF:

0.000164

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000548

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 28, 2023

The c.412C>T (p.R138C) alteration is located in exon 4 (coding exon 4) of the IL11 gene. This alteration results from a C to T substitution at nucleotide position 412, causing the arginine (R) at amino acid position 138 to be replaced by a cysteine (C). 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

Benign

0.28

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.12

M_CAP

Benign

0.040

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.8

D;.;.

REVEL

Benign

0.098

Sift

Uncertain

0.027

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.0040

B;.;B

Vest4

0.47

MVP

0.35

MPC

0.52

ClinPred

0.13

GERP RS

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.34

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

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