NM_001142784.3:c.1-202_1-201delTG

Variant names:

• chr9-34654994-CGT-C
• rs59679449
• NM_001142784.3:c.1-202_1-201delTG

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.1-202_1-201delTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 440,154 control chromosomes in the GnomAD database, including 211 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (118 hom., cov: 0)
  • Exomes 𝑓: 0.11 (93 hom.)
• Consequence: IL11RA NM_001142784.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0460
• 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-CGT-C is Benign according to our data. Variant chr9-34654994-CGT-C is described in ClinVar as Benign. ClinVar VariationId is 1251083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0286 (4258/148726) while in subpopulation EAS AF = 0.0452 (225/4978). AF 95% confidence interval is 0.0404. There are 118 homozygotes in GnomAd4. There are 2337 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 118 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.1-202_1-201delTG		intron	N/A	NP_001136256.1	Q14626-1
	IL11RA	NR_052010.2		n.88-202_88-201delTG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11RA	ENST00000441545.7	TSL:5 MANE Select	c.1-202_1-201delTG		intron	N/A	ENSP00000394391.3	Q14626-1
	IL11RA	ENST00000318041.13	TSL:1	c.1-202_1-201delTG		intron	N/A	ENSP00000326500.8	Q14626-1
	ENSG00000258728	ENST00000556278.1	TSL:5	c.433-202_433-201delTG		intron	N/A	ENSP00000451792.1	G3V4G9

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4259 AN: 148644 Hom.: 118 Cov.: 0

Gnomad AFR AF: 0.00621

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.0128

Gnomad EAS AF: 0.0449

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0161

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0274

GnomAD4 exome AF: 0.110 AC: 32104 AN: 291428 Hom.: 93 AF XY: 0.112 AC XY: 17292 AN XY: 154970

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

African (AFR) AF: 0.0730 AC: 576 AN: 7886

American (AMR) AF: 0.0851 AC: 1228 AN: 14430

Ashkenazi Jewish (ASJ) AF: 0.0665 AC: 576 AN: 8658

East Asian (EAS) AF: 0.187 AC: 3424 AN: 18278

South Asian (SAS) AF: 0.126 AC: 4550 AN: 36136

European-Finnish (FIN) AF: 0.163 AC: 3065 AN: 18806

Middle Eastern (MID) AF: 0.0927 AC: 115 AN: 1240

European-Non Finnish (NFE) AF: 0.0995 AC: 16884 AN: 169616

Other (OTH) AF: 0.103 AC: 1686 AN: 16378

⚠️ 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: 0.0286 AC: 4258 AN: 148726 Hom.: 118 Cov.: 0 AF XY: 0.0322 AC XY: 2337 AN XY: 72488

African (AFR) AF: 0.00622 AC: 252 AN: 40516

American (AMR) AF: 0.0146 AC: 218 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.0128 AC: 44 AN: 3430

East Asian (EAS) AF: 0.0452 AC: 225 AN: 4978

South Asian (SAS) AF: 0.0374 AC: 175 AN: 4684

European-Finnish (FIN) AF: 0.115 AC: 1161 AN: 10054

Middle Eastern (MID) AF: 0.0174 AC: 5 AN: 288

European-Non Finnish (NFE) AF: 0.0307 AC: 2051 AN: 66842

Other (OTH) AF: 0.0272 AC: 56 AN: 2062

Alfa AF: 0.0230 Hom.: 252

ClinVar

ClinVar submissions

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		0.046
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs59679449; hg19: chr9-34654991;