19-55368277-G-A

Position:

• chr19-55368277-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000641.4(IL11):​c.362C>T​(p.Thr121Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,407,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: IL11 NM_000641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31977195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL11	NM_000641.4	c.362C>T	p.Thr121Ile	missense_variant	4/5	ENST00000264563.7
IL11	NM_001267718.2	c.125C>T	p.Thr42Ile	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL11	ENST00000264563.7	c.362C>T	p.Thr121Ile	missense_variant	4/5	1	NM_000641.4	P1
IL11	ENST00000585513.1	c.362C>T	p.Thr121Ile	missense_variant	4/5	1		P1
IL11	ENST00000590625.5	c.125C>T	p.Thr42Ile	missense_variant	3/4	2
IL11	ENST00000587093.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1407736 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 695290

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000273

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;L
MutationTaster	Benign	0.83	N;N;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.3	D;.;.
REVEL	Benign	0.13
Sift	Benign	0.048	D;.;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.98	D;.;D
Vest4		0.22
MutPred		0.59		Gain of catalytic residue at L126 (P = 0.024);.;Gain of catalytic residue at L126 (P = 0.024);
MVP		0.74
MPC		0.11
ClinPred		0.86	D
GERP RS		3.0
Varity_R		0.36
gMVP		0.37

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

Other links and lift over

dbSNP: rs1414373372; hg19: chr19-55879645;