Genetic Variant IL11:c.*1135G>A (chr19-55364872-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000641.4(IL11):c.*1135G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,134 control chromosomes in the GnomAD database, including 5,765 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 5764 hom., cov: 32)

Exomes 𝑓: 0.30 ( 1 hom. )

Consequence

IL11
NM_000641.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.670

Publications

12 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL11	NM_000641.4 link	c.*1135G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000264563.7	NP_000632.1	P20809-1A8K3F7
IL11	NM_001267718.2 link	c.*1135G>A		3_prime_UTR_variant	Exon 4 of 4		NP_001254647.1	P20809-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL11	ENST00000264563.7 link	c.*1135G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_000641.4	ENSP00000264563.1		P20809-1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40660

AN:

152006

Hom.:

5757

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.274

GnomAD4 exome

AF:

0.300

AC:

AN:

Hom.:

Cov.:

AF XY:

0.300

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.267

AC:

40681

AN:

152124

Hom.:

5764

Cov.:

AF XY:

0.264

AC XY:

19660

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.206

AC:

8542

AN:

41496

American (AMR)

AF:

0.234

AC:

3567

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1149

AN:

3468

East Asian (EAS)

AF:

0.157

AC:

814

AN:

5184

South Asian (SAS)

AF:

0.413

AC:

1992

AN:

4822

European-Finnish (FIN)

AF:

0.207

AC:

2190

AN:

10588

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.317

AC:

21568

AN:

67974

Other (OTH)

AF:

0.271

AC:

572

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1512

3024

4537

6049

7561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.300

Hom.:

24966

Bravo

AF:

0.262

Asia WGS

AF:

0.278

AC:

964

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.5

(source)

DANN

Benign

0.45

PhyloP100

-0.67

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over