9-34655737-G-T

Variant names:

• chr9-34655737-G-T
• rs11575576
• NM_001142784.3:c.161+72G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142784.3(IL11RA):​c.161+72G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,289,298 control chromosomes in the GnomAD database, including 113,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11392 hom., cov: 31)
  • Exomes 𝑓: 0.42 (101695 hom.)
• Consequence: IL11RA NM_001142784.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.290
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 9-34655737-G-T is Benign according to our data. Variant chr9-34655737-G-T is described in ClinVar as Benign. ClinVar VariationId is 1231709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 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.161+72G>T		intron	N/A	NP_001136256.1	Q14626-1
	IL11RA	NR_052010.2		n.248+72G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11RA	ENST00000441545.7	TSL:5 MANE Select	c.161+72G>T		intron	N/A	ENSP00000394391.3	Q14626-1
	IL11RA	ENST00000318041.13	TSL:1	c.161+72G>T		intron	N/A	ENSP00000326500.8	Q14626-1
	IL11RA	ENST00000602473.5	TSL:1	c.161+72G>T		intron	N/A	ENSP00000473647.1	Q14626-2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56314 AN: 151696 Hom.: 11375 Cov.: 31

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.417 AC: 473902 AN: 1137484 Hom.: 101695 Cov.: 15 AF XY: 0.416 AC XY: 241070 AN XY: 579168

African (AFR) AF: 0.201 AC: 5545 AN: 27526

American (AMR) AF: 0.305 AC: 12874 AN: 42208

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 11256 AN: 23828

East Asian (EAS) AF: 0.524 AC: 19825 AN: 37846

South Asian (SAS) AF: 0.335 AC: 26255 AN: 78358

European-Finnish (FIN) AF: 0.488 AC: 25604 AN: 52506

Middle Eastern (MID) AF: 0.438 AC: 2226 AN: 5086

European-Non Finnish (NFE) AF: 0.426 AC: 349589 AN: 820458

Other (OTH) AF: 0.417 AC: 20728 AN: 49668

GnomAD4 genome AF: 0.371 AC: 56348 AN: 151814 Hom.: 11392 Cov.: 31 AF XY: 0.374 AC XY: 27737 AN XY: 74192

African (AFR) AF: 0.208 AC: 8593 AN: 41380

American (AMR) AF: 0.368 AC: 5624 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1664 AN: 3470

East Asian (EAS) AF: 0.524 AC: 2699 AN: 5154

South Asian (SAS) AF: 0.346 AC: 1666 AN: 4810

European-Finnish (FIN) AF: 0.486 AC: 5117 AN: 10520

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.438 AC: 29734 AN: 67910

Other (OTH) AF: 0.408 AC: 859 AN: 2106

Alfa AF: 0.248 Hom.: 721

Bravo AF: 0.357

Asia WGS AF: 0.444 AC: 1544 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.40
DANN	Benign	0.51
PhyloP100		-0.29
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: rs11575576; hg19: chr9-34655734; COSMIC: COSV58841330; COSMIC: COSV58841330;