NM_001142784.3:c.100+122T>C

Variant names:

• chr9-34655439-T-C
• rs2812357
• NM_001142784.3:c.100+122T>C

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.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
• Publications: 18 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 -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 VariationId 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.

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.100+122T>C		intron	N/A	NP_001136256.1	Q14626-1
	IL11RA	NR_052010.2		n.187+122T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11RA	ENST00000441545.7	TSL:5 MANE Select	c.100+122T>C		intron	N/A	ENSP00000394391.3	Q14626-1
	IL11RA	ENST00000318041.13	TSL:1	c.100+122T>C		intron	N/A	ENSP00000326500.8	Q14626-1
	IL11RA	ENST00000602473.5	TSL:1	c.100+122T>C		intron	N/A	ENSP00000473647.1	Q14626-2

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

African (AFR) AF: 0.591 AC: 10963 AN: 18550

American (AMR) AF: 0.430 AC: 15018 AN: 34926

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 13095 AN: 20822

East Asian (EAS) AF: 0.535 AC: 17576 AN: 32842

South Asian (SAS) AF: 0.557 AC: 36435 AN: 65454

European-Finnish (FIN) AF: 0.648 AC: 31275 AN: 48256

Middle Eastern (MID) AF: 0.608 AC: 1926 AN: 3166

European-Non Finnish (NFE) AF: 0.590 AC: 265449 AN: 450066

Other (OTH) AF: 0.593 AC: 20925 AN: 35316

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

African (AFR) AF: 0.595 AC: 24667 AN: 41434

American (AMR) AF: 0.516 AC: 7889 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2179 AN: 3468

East Asian (EAS) AF: 0.533 AC: 2745 AN: 5146

South Asian (SAS) AF: 0.559 AC: 2689 AN: 4812

European-Finnish (FIN) AF: 0.653 AC: 6896 AN: 10564

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40136 AN: 67954

Other (OTH) AF: 0.592 AC: 1251 AN: 2112

Alfa AF: 0.582 Hom.: 41172

Bravo AF: 0.575

Asia WGS AF: 0.565 AC: 1962 AN: 3476

ClinVar

ClinVar submissions

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	-0.85
CADD	Benign	2.3
DANN	Benign	0.86
PhyloP100		-0.044
PromoterAI		0.0024	Neutral
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: rs2812357; hg19: chr9-34655436; COSMIC: COSV58841318; COSMIC: COSV58841318;