chr9-34656482-G-A

Variant names:

• chr9-34656482-G-A
• rs11575578
• NM_001142784.3:c.162-257G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001142784.3(IL11RA):​c.162-257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 152,258 control chromosomes in the GnomAD database, including 257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.047 (257 hom., cov: 32)
• Consequence: IL11RA NM_001142784.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0210
• Publications: 10 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-34656482-G-A is Benign according to our data. Variant chr9-34656482-G-A is described in ClinVar as Benign. ClinVar VariationId is 1220727.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.063 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.162-257G>A		intron	N/A	NP_001136256.1	Q14626-1
	IL11RA	NR_052010.2		n.249-257G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11RA	ENST00000441545.7	TSL:5 MANE Select	c.162-257G>A		intron	N/A	ENSP00000394391.3	Q14626-1
	IL11RA	ENST00000318041.13	TSL:1	c.162-257G>A		intron	N/A	ENSP00000326500.8	Q14626-1
	IL11RA	ENST00000602473.5	TSL:1	c.162-257G>A		intron	N/A	ENSP00000473647.1	Q14626-2

Frequencies

GnomAD3 genomes AF: 0.0469 AC: 7141 AN: 152140 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.0685

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.0431

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0469 AC: 7143 AN: 152258 Hom.: 257 Cov.: 32 AF XY: 0.0467 AC XY: 3477 AN XY: 74438

African (AFR) AF: 0.0123 AC: 512 AN: 41550

American (AMR) AF: 0.0476 AC: 729 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 164 AN: 3470

East Asian (EAS) AF: 0.00926 AC: 48 AN: 5186

South Asian (SAS) AF: 0.0684 AC: 330 AN: 4828

European-Finnish (FIN) AF: 0.0672 AC: 712 AN: 10594

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0646 AC: 4395 AN: 68012

Other (OTH) AF: 0.0436 AC: 92 AN: 2112

Alfa AF: 0.0567 Hom.: 45

Bravo AF: 0.0422

Asia WGS AF: 0.0350 AC: 120 AN: 3478

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
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.80
PhyloP100		0.021
Mutation Taster		=100/0	polymorphism (auto)

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: rs11575578; hg19: chr9-34656479;