9-34654994-CGTGTGTGTGTGT-CGTGTGTGTGTGTGTGTGT

Variant names:

• chr9-34654994-C-CGTGTGT
• rs59679449
• NM_001142784.3:c.1-206_1-201dupTGTGTG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001142784.3(IL11RA):​c.1-206_1-201dupTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0012 (0 hom.)
• Consequence: IL11RA NM_001142784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• Publications: 0 publications found

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]

IL11RA Gene-Disease associations (from GenCC):

• craniosynostosis and dental anomalies

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ENSG00000258728 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00278 (414/148934) while in subpopulation AMR AF = 0.00673 (101/15004). AF 95% confidence interval is 0.00567. There are 0 homozygotes in GnomAd4. There are 224 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142784.3. 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
	IL11RA	NM_001142784.3	MANE Select	c.1-206_1-201dupTGTGTG		intron	N/A	NP_001136256.1	Q14626-1
	IL11RA	NR_052010.2		n.88-206_88-201dupTGTGTG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11RA	ENST00000441545.7	TSL:5 MANE Select	c.1-206_1-201dupTGTGTG		intron	N/A	ENSP00000394391.3	Q14626-1
	IL11RA	ENST00000318041.13	TSL:1	c.1-206_1-201dupTGTGTG		intron	N/A	ENSP00000326500.8	Q14626-1
	ENSG00000258728	ENST00000556278.1	TSL:5	c.433-206_433-201dupTGTGTG		intron	N/A	ENSP00000451792.1	G3V4G9

Frequencies

GnomAD3 genomes AF: 0.00278 AC: 414 AN: 148848 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00527

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.00437

Gnomad EAS AF: 0.00160

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00395

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000523

Gnomad OTH AF: 0.000488

GnomAD4 exome AF: 0.00121 AC: 394 AN: 326482 Hom.: 0 Cov.: 0 AF XY: 0.00110 AC XY: 192 AN XY: 174212

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00397 AC: 35 AN: 8810

American (AMR) AF: 0.00882 AC: 142 AN: 16092

Ashkenazi Jewish (ASJ) AF: 0.00223 AC: 21 AN: 9400

East Asian (EAS) AF: 0.00351 AC: 75 AN: 21364

South Asian (SAS) AF: 0.000210 AC: 9 AN: 42896

European-Finnish (FIN) AF: 0.00132 AC: 27 AN: 20400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1344

European-Non Finnish (NFE) AF: 0.000303 AC: 57 AN: 188146

Other (OTH) AF: 0.00155 AC: 28 AN: 18030

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00278 AC: 414 AN: 148934 Hom.: 0 Cov.: 0 AF XY: 0.00308 AC XY: 224 AN XY: 72620

African (AFR) AF: 0.00528 AC: 214 AN: 40536

American (AMR) AF: 0.00673 AC: 101 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.00437 AC: 15 AN: 3432

East Asian (EAS) AF: 0.00160 AC: 8 AN: 4988

South Asian (SAS) AF: 0.00 AC: 0 AN: 4692

European-Finnish (FIN) AF: 0.00395 AC: 40 AN: 10124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000523 AC: 35 AN: 66906

Other (OTH) AF: 0.000484 AC: 1 AN: 2066

Alfa AF: 0.00157 Hom.: 252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs59679449; hg19: chr9-34654991;