19-55366042-C-T

Variant names:

• chr19-55366042-C-T
• rs201003688
• NM_000641.4:c.565G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000641.4(IL11):​c.565G>A​(p.Val189Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000268 in 1,603,658 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: 𝑓 0.000046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: IL11 NM_000641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16565257).

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.565G>A	p.Val189Met	missense	Exon 5 of 5	NP_000632.1	A8K3F7
	IL11	NM_001267718.2		c.328G>A	p.Val110Met	missense	Exon 4 of 4	NP_001254647.1	P20809-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11	ENST00000264563.7	TSL:1 MANE Select	c.565G>A	p.Val189Met	missense	Exon 5 of 5	ENSP00000264563.1	P20809-1
	IL11	ENST00000585513.1	TSL:1	c.565G>A	p.Val189Met	missense	Exon 5 of 5	ENSP00000467355.1	P20809-1
	IL11	ENST00000590625.5	TSL:2	c.328G>A	p.Val110Met	missense	Exon 4 of 4	ENSP00000465705.1	P20809-2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152150 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000401 AC: 9 AN: 224508 AF XY: 0.0000409

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000577

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000305

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000248 AC: 36 AN: 1451390 Hom.: 0 Cov.: 32 AF XY: 0.0000264 AC XY: 19 AN XY: 721016

African (AFR) AF: 0.0000300 AC: 1 AN: 33332

American (AMR) AF: 0.0000917 AC: 4 AN: 43626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25824

East Asian (EAS) AF: 0.000279 AC: 11 AN: 39368

South Asian (SAS) AF: 0.000119 AC: 10 AN: 84234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 0.00000722 AC: 8 AN: 1108220

Other (OTH) AF: 0.0000333 AC: 2 AN: 59992

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152268 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74438

African (AFR) AF: 0.0000481 AC: 2 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000682 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000583 AC: 7

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.26
Sift	Benign	0.11	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.36
MVP		0.50
MPC		0.50
ClinPred		0.34	T
GERP RS		4.6
Varity_R		0.25
gMVP		0.38
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs201003688; hg19: chr19-55877410; COSMIC: COSV99215040; COSMIC: COSV99215040;