9-34655439-T-C

Position:

• chr9-34655439-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142784.3(IL11RA):​c.100+122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 861,380 control chromosomes in the GnomAD database, including 147,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26199 hom., cov: 30)
  • Exomes 𝑓: 0.58 (121178 hom.)
• Consequence: IL11RA NM_001142784.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0440

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]

ENSG00000258728 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-34655439-T-C is Benign according to our data. Variant chr9-34655439-T-C is described in ClinVar as [Benign]. Clinvar id is 1179216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL11RA	NM_001142784.3	c.100+122T>C		intron_variant		ENST00000441545.7	NP_001136256.1
IL11RA	NR_052010.2	n.187+122T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL11RA	ENST00000441545.7	c.100+122T>C		intron_variant		5	NM_001142784.3	ENSP00000394391.3
ENSG00000258728	ENST00000556278.1	c.532+122T>C		intron_variant		5		ENSP00000451792.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89008 AN: 151864 Hom.: 26164 Cov.: 30

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.582 AC: 412662 AN: 709398 Hom.: 121178 Cov.: 9 AF XY: 0.581 AC XY: 217528 AN XY: 374450

Gnomad4 AFR exome AF: 0.591

Gnomad4 AMR exome AF: 0.430

Gnomad4 ASJ exome AF: 0.629

Gnomad4 EAS exome AF: 0.535

Gnomad4 SAS exome AF: 0.557

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.593

GnomAD4 genome AF: 0.586 AC: 89100 AN: 151982 Hom.: 26199 Cov.: 30 AF XY: 0.586 AC XY: 43536 AN XY: 74278

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.592

Alfa AF: 0.583 Hom.: 32864

Bravo AF: 0.575

Asia WGS AF: 0.565 AC: 1962 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs2812357; hg19: chr9-34655436; COSMIC: COSV58841318; COSMIC: COSV58841318;