chr9-34654994-C-CGTGT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001142784.3(IL11RA):​c.1-204_1-201dupTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (36 hom., cov: 0)
  • Exomes 𝑓: 0.0040 (1 hom.)
• Consequence: IL11RA NM_001142784.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-34654994-C-CGTGT is Benign according to our data. Variant chr9-34654994-C-CGTGT is described in ClinVar as Likely_benign. ClinVar VariationId is 1186856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0145 (2161/148912) while in subpopulation AFR AF = 0.046 (1865/40522). AF 95% confidence interval is 0.0443. There are 36 homozygotes in GnomAd4. There are 992 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

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.1-204_1-201dupTGTG		intron	N/A	NP_001136256.1	Q14626-1
	IL11RA	NR_052010.2		n.88-204_88-201dupTGTG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11RA	ENST00000441545.7	TSL:5 MANE Select	c.1-204_1-201dupTGTG		intron	N/A	ENSP00000394391.3	Q14626-1
	IL11RA	ENST00000318041.13	TSL:1	c.1-204_1-201dupTGTG		intron	N/A	ENSP00000326500.8	Q14626-1
	ENSG00000258728	ENST00000556278.1	TSL:5	c.433-204_433-201dupTGTG		intron	N/A	ENSP00000451792.1	G3V4G9

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2161 AN: 148826 Hom.: 36 Cov.: 0

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00808

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000400

Gnomad SAS AF: 0.00553

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00645

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.0122

GnomAD4 exome AF: 0.00400 AC: 1304 AN: 325936 Hom.: 1 Cov.: 0 AF XY: 0.00390 AC XY: 678 AN XY: 173922

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

African (AFR) AF: 0.0460 AC: 404 AN: 8792

American (AMR) AF: 0.00535 AC: 86 AN: 16062

Ashkenazi Jewish (ASJ) AF: 0.000854 AC: 8 AN: 9366

East Asian (EAS) AF: 0.000609 AC: 13 AN: 21362

South Asian (SAS) AF: 0.00523 AC: 224 AN: 42836

European-Finnish (FIN) AF: 0.000687 AC: 14 AN: 20370

Middle Eastern (MID) AF: 0.00674 AC: 9 AN: 1336

European-Non Finnish (NFE) AF: 0.00236 AC: 443 AN: 187810

Other (OTH) AF: 0.00572 AC: 103 AN: 18002

⚠️ 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: 0.0145 AC: 2161 AN: 148912 Hom.: 36 Cov.: 0 AF XY: 0.0137 AC XY: 992 AN XY: 72610

African (AFR) AF: 0.0460 AC: 1865 AN: 40522

American (AMR) AF: 0.00807 AC: 121 AN: 15000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.000401 AC: 2 AN: 4988

South Asian (SAS) AF: 0.00554 AC: 26 AN: 4692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10124

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.00181 AC: 121 AN: 66902

Other (OTH) AF: 0.0121 AC: 25 AN: 2066

Alfa AF: 0.000278 Hom.: 252

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism

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;