NM_000641.4:c.246G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• 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: Benign. The variant received -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.

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

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57432 AN: 151760 Hom.: 13522 Cov.: 31

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

GnomAD2 exomes AF: 0.477 AC: 116725 AN: 244750 AF XY: 0.481

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 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.: 42 AF XY: 0.474 AC XY: 343853 AN XY: 725338

African (AFR) AF: 0.0726 AC: 2429 AN: 33466

American (AMR) AF: 0.496 AC: 21958 AN: 44276

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 10661 AN: 26052

East Asian (EAS) AF: 0.740 AC: 29303 AN: 39620

South Asian (SAS) AF: 0.476 AC: 40792 AN: 85714

European-Finnish (FIN) AF: 0.571 AC: 30377 AN: 53176

Middle Eastern (MID) AF: 0.424 AC: 2437 AN: 5754

European-Non Finnish (NFE) AF: 0.472 AC: 524019 AN: 1110300

Other (OTH) AF: 0.456 AC: 27451 AN: 60254

GnomAD4 genome AF: 0.378 AC: 57398 AN: 151878 Hom.: 13509 Cov.: 31 AF XY: 0.388 AC XY: 28770 AN XY: 74184

African (AFR) AF: 0.0903 AC: 3742 AN: 41452

American (AMR) AF: 0.447 AC: 6824 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1413 AN: 3470

East Asian (EAS) AF: 0.723 AC: 3718 AN: 5146

South Asian (SAS) AF: 0.461 AC: 2215 AN: 4802

European-Finnish (FIN) AF: 0.571 AC: 6015 AN: 10536

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.473 AC: 32123 AN: 67912

Other (OTH) AF: 0.375 AC: 791 AN: 2108

Alfa AF: 0.444 Hom.: 50452

Bravo AF: 0.356

Asia WGS AF: 0.500 AC: 1739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.0
DANN	Benign	0.27
PhyloP100		-6.0
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV52772588;