chr19-55364872-C-T

Position:

• chr19-55364872-C-T

Variant summary

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

The NM_000641.4(IL11):​c.*1135G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,134 control chromosomes in the GnomAD database, including 5,765 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 0.27 (5764 hom., cov: 32)
  • Exomes 𝑓: 0.30 (1 hom.)
• Consequence: IL11 NM_000641.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL11	NM_000641.4	c.*1135G>A		3_prime_UTR_variant	5/5	ENST00000264563.7	NP_000632.1
IL11	NM_001267718.2	c.*1135G>A		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.*1135G>A		3_prime_UTR_variant	5/5	1	NM_000641.4	ENSP00000264563	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40660 AN: 152006 Hom.: 5757 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.300 AC: 3 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.375

GnomAD4 genome AF: 0.267 AC: 40681 AN: 152124 Hom.: 5764 Cov.: 32 AF XY: 0.264 AC XY: 19660 AN XY: 74356

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.271

Alfa AF: 0.312 Hom.: 9580

Bravo AF: 0.262

Asia WGS AF: 0.278 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.45

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: rs2298885; hg19: chr19-55876240; COSMIC: COSV52773661; COSMIC: COSV52773661;