rs1042506

Positions:

• chr19-55365743-A-C

Variant summary

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

The NM_000641.4(IL11):​c.*264T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 500,052 control chromosomes in the GnomAD database, including 4,328 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 0.13 (1345 hom., cov: 30)
  • Exomes 𝑓: 0.12 (2983 hom.)
• Consequence: IL11 NM_000641.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL11	NM_000641.4	c.*264T>G		3_prime_UTR_variant	5/5	ENST00000264563.7	NP_000632.1
IL11	NM_001267718.2	c.*264T>G		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.*264T>G		3_prime_UTR_variant	5/5	1	NM_000641.4	ENSP00000264563	P1
IL11	ENST00000585513.1	c.*264T>G		3_prime_UTR_variant	5/5	1		ENSP00000467355	P1
IL11	ENST00000590625.5	c.*264T>G		3_prime_UTR_variant	4/4	2		ENSP00000465705

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19463 AN: 151764 Hom.: 1342 Cov.: 30

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00581

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.123 AC: 42801 AN: 348170 Hom.: 2983 Cov.: 3 AF XY: 0.119 AC XY: 21854 AN XY: 184240

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.0844

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.00307

Gnomad4 SAS exome AF: 0.0733

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.128 AC: 19481 AN: 151882 Hom.: 1345 Cov.: 30 AF XY: 0.128 AC XY: 9503 AN XY: 74206

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0849

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.00622

Gnomad4 SAS AF: 0.0729

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.124

Alfa AF: 0.135 Hom.: 1154

Bravo AF: 0.123

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	10
DANN	Benign	0.81

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: rs1042506; hg19: chr19-55877111;