Genetic Variant IL11:p.Ala82Ala (chr19-55368504-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000641.4(IL11):c.246G>A(p.Ala82Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,610,490 control chromosomes in the GnomAD database, including 181,537 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 0.38 ( 13509 hom., cov: 31)

Exomes 𝑓: 0.47 ( 168028 hom. )

Consequence

IL11
NM_000641.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.02

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP7

Synonymous conserved (PhyloP=-6.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL11	NM_000641.4 link	c.246G>A	p.Ala82Ala	synonymous_variant	Exon 3 of 5	ENST00000264563.7	NP_000632.1	P20809-1A8K3F7
IL11	NM_001267718.2 link	c.9G>A	p.Ala3Ala	synonymous_variant	Exon 2 of 4		NP_001254647.1	P20809-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL11	ENST00000264563.7 link	c.246G>A	p.Ala82Ala	synonymous_variant	Exon 3 of 5	1	NM_000641.4	ENSP00000264563.1	P20809-1
IL11	ENST00000585513.1 link	c.246G>A	p.Ala82Ala	synonymous_variant	Exon 3 of 5	1		ENSP00000467355.1	P20809-1
IL11	ENST00000590625.5 link	c.9G>A	p.Ala3Ala	synonymous_variant	Exon 2 of 4	2		ENSP00000465705.1	P20809-2
IL11	ENST00000587093.1 link	c.9G>A	p.Ala3Ala	synonymous_variant	Exon 2 of 3	2		ENSP00000468663.1	K7ESD5

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57432

AN:

151760

Hom.:

13522

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0905

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.723

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.473

Gnomad OTH

AF:

0.379

GnomAD3 exomes

AF:

0.477

AC:

116725

AN:

244750

Hom.:

29827

AF XY:

0.481

AC XY:

63721

AN XY:

132464

show subpopulations

Gnomad AFR exome

AF:

0.0757

Gnomad AMR exome

AF:

0.502

Gnomad ASJ exome

AF:

0.408

Gnomad EAS exome

AF:

0.727

Gnomad SAS exome

AF:

0.469

Gnomad FIN exome

AF:

0.567

Gnomad NFE exome

AF:

0.478

Gnomad OTH exome

AF:

0.456

GnomAD4 exome

AF:

0.473

AC:

689427

AN:

1458612

Hom.:

168028

Cov.:

AF XY:

0.474

AC XY:

343853

AN XY:

725338

show subpopulations

Gnomad4 AFR exome

AF:

0.0726

Gnomad4 AMR exome

AF:

0.496

Gnomad4 ASJ exome

AF:

0.409

Gnomad4 EAS exome

AF:

0.740

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.571

Gnomad4 NFE exome

AF:

0.472

Gnomad4 OTH exome

AF:

0.456

GnomAD4 genome

AF:

0.378

AC:

57398

AN:

151878

Hom.:

13509

Cov.:

AF XY:

0.388

AC XY:

28770

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.0903

Gnomad4 AMR

AF:

0.447

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.723

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.473

Gnomad4 OTH

AF:

0.375

Alfa

AF:

0.448

Hom.:

21503

Bravo

AF:

0.356

Asia WGS

AF:

0.500

AC:

1739

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.0

DANN

Benign

0.27

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over