chr19-55368301-C-T

Position:

chr19-55368301-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000641.4(IL11):c.338G>A(p.Arg113Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000222 in 1,579,428 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: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

IL11
NM_000641.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.105

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12710917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL11	NM_000641.4 linkuse as main transcript	c.338G>A	p.Arg113Gln	missense_variant	4/5	ENST00000264563.7	NP_000632.1	P20809-1A8K3F7
IL11	NM_001267718.2 linkuse as main transcript	c.101G>A	p.Arg34Gln	missense_variant	3/4		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.338G>A	p.Arg113Gln	missense_variant	4/5	1	NM_000641.4	ENSP00000264563.1	P20809-1
IL11	ENST00000585513.1 linkuse as main transcript	c.338G>A	p.Arg113Gln	missense_variant	4/5	1		ENSP00000467355.1	P20809-1
IL11	ENST00000590625.5 linkuse as main transcript	c.101G>A	p.Arg34Gln	missense_variant	3/4	2		ENSP00000465705.1	P20809-2
IL11	ENST00000587093.1 linkuse as main transcript	c.101G>A	p.Arg34Gln	missense_variant	3/3	2		ENSP00000468663.1	K7ESD5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD3 exomes

AF:

0.0000507

AC:

AN:

197172

Hom.:

AF XY:

0.0000749

AC XY:

AN XY:

106794

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000674

Gnomad SAS exome

AF:

0.000312

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000198

GnomAD4 exome

AF:

0.0000231

AC:

AN:

1427364

Hom.:

Cov.:

AF XY:

0.0000382

AC XY:

AN XY:

706620

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000264

Gnomad4 SAS exome

AF:

0.000342

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.14e-7

Gnomad4 OTH exome

AF:

0.0000339

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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:

0.0000282

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000249

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 19, 2023

The c.338G>A (p.R113Q) 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 338, causing the arginine (R) at amino acid position 113 to be replaced by a glutamine (Q). 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

-0.49

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.;T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.074

LIST_S2

Uncertain

0.87

.;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.;L;.

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.0

D;.;.;.

REVEL

Benign

0.043

Sift

Uncertain

0.0090

D;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.039

B;.;B;.

Vest4

0.32

MutPred

0.70

Loss of MoRF binding (P = 0.0221);.;Loss of MoRF binding (P = 0.0221);.;

MVP

0.46

MPC

0.53

ClinPred

0.12

GERP RS

3.0

Varity_R

0.46

gMVP

0.35

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