Variant 19-55368226-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000641.4(IL11):c.413G>A(p.Arg138His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000058 in 1,533,562 control chromosomes in the GnomAD database, including 2 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R138C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000050 ( 1 hom. )

Consequence

IL11
NM_000641.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.11

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.105944484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL11	NM_000641.4 linkuse as main transcript	c.413G>A	p.Arg138His	missense_variant	4/5	ENST00000264563.7
IL11	NM_001267718.2 linkuse as main transcript	c.176G>A	p.Arg59His	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL11	ENST00000264563.7 linkuse as main transcript	c.413G>A	p.Arg138His	missense_variant	4/5	1	NM_000641.4	P1	P20809-1
IL11	ENST00000585513.1 linkuse as main transcript	c.413G>A	p.Arg138His	missense_variant	4/5	1		P1	P20809-1
IL11	ENST00000590625.5 linkuse as main transcript	c.176G>A	p.Arg59His	missense_variant	3/4	2			P20809-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000554

AC:

AN:

144346

Hom.:

AF XY:

0.0000257

AC XY:

AN XY:

77798

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000820

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000931

Gnomad SAS exome

AF:

0.0000444

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000557

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.0000499

AC:

AN:

1381476

Hom.:

Cov.:

AF XY:

0.0000486

AC XY:

AN XY:

678394

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000567

Gnomad4 SAS exome

AF:

0.0000381

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000487

Gnomad4 OTH exome

AF:

0.000140

GnomAD4 genome

AF:

0.000132

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000475

Bravo

AF:

0.0000907

Asia WGS

AF:

0.00520

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

Oct 22, 2021

The c.413G>A (p.R138H) alteration is located in exon 4 (coding exon 4) of the IL11 gene. This alteration results from a G to A substitution at nucleotide position 413, causing the arginine (R) at amino acid position 138 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

T;.;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.042

M_CAP

Benign

0.022

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.1

N;.;.

REVEL

Benign

0.12

Sift

Benign

0.034

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.96

D;.;D

Vest4

0.26

MutPred

0.52

Loss of MoRF binding (P = 0.0477);.;Loss of MoRF binding (P = 0.0477);

MVP

0.57

MPC

0.12

ClinPred

0.092

GERP RS

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.23

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