Variant 19-55368855-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000264563.7(IL11):c.94T>G(p.Ser32Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,583,132 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

IL11
ENST00000264563.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.752

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=0.0071247816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL11	NM_000641.4 linkuse as main transcript	c.94T>G	p.Ser32Ala	missense_variant	2/5	ENST00000264563.7	NP_000632.1	P20809-1A8K3F7
IL11	NM_001267718.2 linkuse as main transcript	c.-57-286T>G		intron_variant			NP_001254647.1	P20809-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL11	ENST00000264563.7 linkuse as main transcript	c.94T>G	p.Ser32Ala	missense_variant	2/5	1	NM_000641.4	ENSP00000264563.1		P20809-1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000266

AC:

AN:

195654

Hom.:

AF XY:

0.000257

AC XY:

AN XY:

105218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00434

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000129

Gnomad OTH exome

AF:

0.000607

GnomAD4 exome

AF:

0.000130

AC:

186

AN:

1431054

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

101

AN XY:

708554

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00496

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000310

Gnomad4 OTH exome

AF:

0.000422

GnomAD4 genome

AF:

0.000118

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000428

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.000109

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

Jun 11, 2021

The c.94T>G (p.S32A) alteration is located in exon 2 (coding exon 2) of the IL11 gene. This alteration results from a T to G substitution at nucleotide position 94, causing the serine (S) at amino acid position 32 to be replaced by an alanine (A). 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

0.072

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.051

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.34

.;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0071

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.97

N;.

REVEL

Benign

0.055

Sift

Benign

0.15

T;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0

B;B

Vest4

0.13

MVP

0.23

MPC

0.079

ClinPred

0.015

GERP RS

-3.6

Varity_R

0.15

gMVP

0.20

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