rs1126760

Positions:

• chr19-55364706-G-A
• chr19-55364706-G-C
• chr19-55364706-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000641.4(IL11):​c.*1301C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 151,954 control chromosomes in the GnomAD database, including 42,451 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 0.74 (42448 hom., cov: 31)
  • Exomes 𝑓: 0.80 (3 hom.)
• Consequence: IL11 NM_000641.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL11	NM_000641.4	c.*1301C>T		3_prime_UTR_variant	5/5	ENST00000264563.7	NP_000632.1
IL11	NM_001267718.2	c.*1301C>T		3_prime_UTR_variant	4/4		NP_001254647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL11	ENST00000264563.7	c.*1301C>T		3_prime_UTR_variant	5/5	1	NM_000641.4	ENSP00000264563.1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113047 AN: 151826 Hom.: 42431 Cov.: 31

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.800 AC: 8 AN: 10 Hom.: 3 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

Gnomad4 FIN exome AF: 0.833

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.744 AC: 113104 AN: 151944 Hom.: 42448 Cov.: 31 AF XY: 0.746 AC XY: 55422 AN XY: 74254

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.851

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.721

Alfa AF: 0.770 Hom.: 41313

Bravo AF: 0.732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.58

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: rs1126760; hg19: chr19-55876074;