19-55368504-C-G

Variant names:

• chr19-55368504-C-G
• rs1126757
• NM_000641.4:c.246G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000641.4(IL11):​c.246G>C​(p.Ala82Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,332 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IL11 NM_000641.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.02
• Publications: 53 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-6.02 with no splicing effect.

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.246G>C	p.Ala82Ala	synonymous	Exon 3 of 5	NP_000632.1	A8K3F7
	IL11	NM_001267718.2		c.9G>C	p.Ala3Ala	synonymous	Exon 2 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.246G>C	p.Ala82Ala	synonymous	Exon 3 of 5	ENSP00000264563.1	P20809-1
	IL11	ENST00000585513.1	TSL:1	c.246G>C	p.Ala82Ala	synonymous	Exon 3 of 5	ENSP00000467355.1	P20809-1
	IL11	ENST00000590625.5	TSL:2	c.9G>C	p.Ala3Ala	synonymous	Exon 2 of 4	ENSP00000465705.1	P20809-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244750 AF XY: 0.00000755

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000907

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459332 Hom.: 0 Cov.: 42 AF XY: 0.00000276 AC XY: 2 AN XY: 725706

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 85792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110798

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 50452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-6.0

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: rs1126757; hg19: chr19-55879872;