Genetic Variant NM_000641.4:c.457C>T (chr19-55366150-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000641.4(IL11):c.457C>T(p.Pro153Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,507,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

IL11
NM_000641.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.449

Publications

3 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.043596536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11	NM_000641.4	MANE Select	c.457C>T	p.Pro153Ser	missense	Exon 5 of 5	NP_000632.1	A8K3F7
	IL11	NM_001267718.2		c.220C>T	p.Pro74Ser	missense	Exon 4 of 4	NP_001254647.1	P20809-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL11	ENST00000264563.7	TSL:1 MANE Select	c.457C>T	p.Pro153Ser	missense	Exon 5 of 5	ENSP00000264563.1	P20809-1
IL11	ENST00000585513.1	TSL:1	c.457C>T	p.Pro153Ser	missense	Exon 5 of 5	ENSP00000467355.1	P20809-1
IL11	ENST00000590625.5	TSL:2	c.220C>T	p.Pro74Ser	missense	Exon 4 of 4	ENSP00000465705.1	P20809-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152014

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:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000848

AC:

AN:

117954

AF XY:

0.0000772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000216

Gnomad OTH exome

AF:

0.000291

GnomAD4 exome

AF:

0.000131

AC:

177

AN:

1355216

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

669080

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29738

American (AMR)

AF:

0.00

AC:

AN:

29058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23524

East Asian (EAS)

AF:

0.000113

AC:

AN:

35398

South Asian (SAS)

AF:

0.00

AC:

AN:

75942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3956

European-Non Finnish (NFE)

AF:

0.000153

AC:

161

AN:

1054342

Other (OTH)

AF:

0.000214

AC:

AN:

56060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41376

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67982

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000604

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000587

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.9

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.067

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.65

M_CAP

Benign

0.018

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-0.45

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.55

REVEL

Benign

0.032

Sift

Benign

0.70

Sift4G

Benign

0.084

Polyphen

0.0010

Vest4

0.11

MutPred

0.40

Loss of catalytic residue at P153 (P = 0.0055)

MVP

0.17

MPC

0.098

ClinPred

0.018

GERP RS

-2.9

Varity_R

0.13

gMVP

0.24

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over