9-34655016-T-TGTGC

Variant names:

• chr9-34655016-T-TGTGC
• rs1020616428
• NM_001142784.3:c.1-201_1-200insTGCG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001142784.3(IL11RA):​c.1-201_1-200insTGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00692 in 557,548 control chromosomes in the GnomAD database, including 108 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (104 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (4 hom.)
• Consequence: IL11RA NM_001142784.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.359
• 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, ClinGen, Ambry Genetics, G2P

ENSG00000258728 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-34655016-T-TGTGC is Benign according to our data. Variant chr9-34655016-T-TGTGC is described in ClinVar as Benign. ClinVar VariationId is 1290220.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.071 is higher than 0.05.

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.1-201_1-200insTGCG		intron	N/A	NP_001136256.1	Q14626-1
	IL11RA	NR_052010.2		n.88-201_88-200insTGCG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11RA	ENST00000441545.7	TSL:5 MANE Select	c.1-201_1-200insTGCG		intron	N/A	ENSP00000394391.3	Q14626-1
	IL11RA	ENST00000318041.13	TSL:1	c.1-201_1-200insTGCG		intron	N/A	ENSP00000326500.8	Q14626-1
	ENSG00000258728	ENST00000556278.1	TSL:5	c.433-201_433-200insTGCG		intron	N/A	ENSP00000451792.1	G3V4G9

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3135 AN: 150018 Hom.: 104 Cov.: 31

Gnomad AFR AF: 0.0732

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00672

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000223

Gnomad OTH AF: 0.0154

GnomAD4 exome AF: 0.00175 AC: 712 AN: 407414 Hom.: 4 Cov.: 0 AF XY: 0.00151 AC XY: 328 AN XY: 217004

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

African (AFR) AF: 0.0467 AC: 512 AN: 10974

American (AMR) AF: 0.00283 AC: 64 AN: 22610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12700

East Asian (EAS) AF: 0.00 AC: 0 AN: 25600

South Asian (SAS) AF: 0.000490 AC: 24 AN: 49018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27902

Middle Eastern (MID) AF: 0.00116 AC: 2 AN: 1726

European-Non Finnish (NFE) AF: 0.000141 AC: 33 AN: 234332

Other (OTH) AF: 0.00341 AC: 77 AN: 22552

⚠️ 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: 0.0210 AC: 3146 AN: 150134 Hom.: 104 Cov.: 31 AF XY: 0.0199 AC XY: 1461 AN XY: 73260

African (AFR) AF: 0.0732 AC: 2997 AN: 40932

American (AMR) AF: 0.00671 AC: 102 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5078

South Asian (SAS) AF: 0.00 AC: 0 AN: 4744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10150

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

European-Non Finnish (NFE) AF: 0.000223 AC: 15 AN: 67306

Other (OTH) AF: 0.0153 AC: 32 AN: 2098

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: 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		0.36
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: rs1020616428; hg19: chr9-34655013;