Variant 19-55368319-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000264563.7(IL11):c.320A>T(p.His107Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000605 in 1,595,838 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00064 ( 2 hom. )

Consequence

IL11
ENST00000264563.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.340

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 -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL11	NM_000641.4 linkuse as main transcript	c.320A>T	p.His107Leu	missense_variant	4/5	ENST00000264563.7	NP_000632.1	P20809-1A8K3F7
IL11	NM_001267718.2 linkuse as main transcript	c.83A>T	p.His28Leu	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.320A>T	p.His107Leu	missense_variant	4/5	1	NM_000641.4	ENSP00000264563.1	P20809-1
IL11	ENST00000585513.1 linkuse as main transcript	c.320A>T	p.His107Leu	missense_variant	4/5	1		ENSP00000467355.1	P20809-1
IL11	ENST00000590625.5 linkuse as main transcript	c.83A>T	p.His28Leu	missense_variant	3/4	2		ENSP00000465705.1	P20809-2
IL11	ENST00000587093.1 linkuse as main transcript	c.83A>T	p.His28Leu	missense_variant	3/3	2		ENSP00000468663.1	K7ESD5

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000544

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000252

AC:

AN:

222208

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

120354

show subpopulations

Gnomad AFR exome

AF:

0.0000744

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000545

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.000640

AC:

924

AN:

1443760

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

423

AN XY:

716062

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000581

Gnomad4 NFE exome

AF:

0.000818

Gnomad4 OTH exome

AF:

0.000285

GnomAD4 genome

AF:

0.000270

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000469

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000207

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

Jul 26, 2021

The c.320A>T (p.H107L) alteration is located in exon 4 (coding exon 4) of the IL11 gene. This alteration results from a A to T substitution at nucleotide position 320, causing the histidine (H) at amino acid position 107 to be replaced by a leucine (L). 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

0.58

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.31

T;.;T;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.068

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.69

.;T;T;T

M_CAP

Benign

0.061

MetaRNN

Uncertain

0.65

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;L;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-10

D;.;.;.

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

D;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.65

MVP

0.68

MPC

0.56

ClinPred

0.97

GERP RS

3.9

Varity_R

0.92

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