NM_000641.4:c.317G>C

Variant names:

• chr19-55368322-C-G
• NM_000641.4:c.317G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000641.4(IL11):​c.317G>C​(p.Arg106Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,124 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IL11 NM_000641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL11	NM_000641.4	c.317G>C	p.Arg106Pro	missense_variant	Exon 4 of 5	ENST00000264563.7	NP_000632.1
IL11	NM_001267718.2	c.80G>C	p.Arg27Pro	missense_variant	Exon 3 of 4		NP_001254647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL11	ENST00000264563.7	c.317G>C	p.Arg106Pro	missense_variant	Exon 4 of 5	1	NM_000641.4	ENSP00000264563.1
IL11	ENST00000585513.1	c.317G>C	p.Arg106Pro	missense_variant	Exon 4 of 5	1		ENSP00000467355.1
IL11	ENST00000590625.5	c.80G>C	p.Arg27Pro	missense_variant	Exon 3 of 4	2		ENSP00000465705.1
IL11	ENST00000587093.1	c.80G>C	p.Arg27Pro	missense_variant	Exon 3 of 3	2		ENSP00000468663.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445124 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 716878

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;.;T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.79	.;T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;L;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.3	D;.;.;.
REVEL	Benign	0.28
Sift	Uncertain	0.029	D;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.97	D;.;D;.
Vest4		0.38
MutPred		0.67		Loss of MoRF binding (P = 8e-04);.;Loss of MoRF binding (P = 8e-04);.;
MVP		0.72
MPC		0.50
ClinPred		0.90	D
GERP RS		2.8
Varity_R		0.92
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55879690;