9-34654994-CGTGTGTGTGTGT-CGTGTGTGT

Variant names:

• chr9-34654994-CGTGT-C
• rs59679449
• NM_001142784.3:c.1-204_1-201delTGTG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001142784.3(IL11RA):​c.1-204_1-201delTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 469,788 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0035 (0 hom.)
• Consequence: IL11RA NM_001142784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

Genes affected

IL11RA (HGNC:5967): (interleukin 11 receptor subunit alpha) Interleukin 11 is a stromal cell-derived cytokine that belongs to a family of pleiotropic and redundant cytokines that use the gp130 transducing subunit in their high affinity receptors. This gene encodes the IL-11 receptor, which is a member of the hematopoietic cytokine receptor family. This particular receptor is very similar to ciliary neurotrophic factor, since both contain an extracellular region with a 2-domain structure composed of an immunoglobulin-like domain and a cytokine receptor-like domain. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

ENSG00000258728 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00346 (1109/320868) while in subpopulation EAS AF= 0.00769 (160/20794). AF 95% confidence interval is 0.00672. There are 0 homozygotes in gnomad4_exome. There are 552 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL11RA	NM_001142784.3	c.1-204_1-201delTGTG		intron_variant	Intron 1 of 12	ENST00000441545.7	NP_001136256.1
IL11RA	NR_052010.2	n.88-204_88-201delTGTG		intron_variant	Intron 1 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL11RA	ENST00000441545.7	c.1-223_1-220delGTGT		intron_variant	Intron 1 of 12	5	NM_001142784.3	ENSP00000394391.3
ENSG00000258728	ENST00000556278.1	c.433-223_433-220delGTGT		intron_variant	Intron 4 of 7	5		ENSP00000451792.1

Frequencies

GnomAD3 genomes AF: 0.000222 AC: 33 AN: 148834 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00180

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.0000988

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000897

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00346 AC: 1109 AN: 320868 Hom.: 0 AF XY: 0.00322 AC XY: 552 AN XY: 171208

Gnomad4 AFR exome AF: 0.00127

Gnomad4 AMR exome AF: 0.00335

Gnomad4 ASJ exome AF: 0.00301

Gnomad4 EAS exome AF: 0.00769

Gnomad4 SAS exome AF: 0.00198

Gnomad4 FIN exome AF: 0.00567

Gnomad4 NFE exome AF: 0.00317

Gnomad4 OTH exome AF: 0.00378

GnomAD4 genome AF: 0.000222 AC: 33 AN: 148920 Hom.: 0 Cov.: 0 AF XY: 0.000289 AC XY: 21 AN XY: 72610

Gnomad4 AFR AF: 0.000247

Gnomad4 AMR AF: 0.000333

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00180

Gnomad4 SAS AF: 0.000426

Gnomad4 FIN AF: 0.0000988

Gnomad4 NFE AF: 0.0000897

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs59679449; hg19: chr9-34654991;