dbSNP rs1061758: IL11RA:c.-1+100A>G (chr9-34652333-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142784.3(IL11RA):c.-1+100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 153,394 control chromosomes in the GnomAD database, including 45,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.76 ( 44883 hom., cov: 31)

Exomes 𝑓: 0.87 ( 515 hom. )

Consequence

IL11RA
NM_001142784.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.895

Publications

12 publications found

Variant links:

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

IL11RA links:

ENSG00000258728 (HGNC:):

ENSG00000258728 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 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.-1+100A>G		intron	N/A	NP_001136256.1	Q14626-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL11RA	ENST00000441545.7	TSL:5 MANE Select	c.-1+100A>G	intron	N/A	ENSP00000394391.3	Q14626-1
ENSG00000258728	ENST00000556278.1	TSL:5	c.433-2885A>G	intron	N/A	ENSP00000451792.1	G3V4G9
IL11RA	ENST00000957054.1		c.-1+100A>G	intron	N/A	ENSP00000627113.1

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

115895

AN:

151910

Hom.:

44844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.809

Gnomad AMR

AF:

0.711

Gnomad ASJ

AF:

0.860

Gnomad EAS

AF:

0.601

Gnomad SAS

AF:

0.799

Gnomad FIN

AF:

0.872

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.834

Gnomad OTH

AF:

0.765

GnomAD4 exome

AF:

0.867

AC:

1184

AN:

1366

Hom.:

515

AF XY:

0.862

AC XY:

674

AN XY:

782

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.375

AC:

AN:

South Asian (SAS)

AF:

0.944

AC:

AN:

European-Finnish (FIN)

AF:

0.875

AC:

971

AN:

1110

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.851

AC:

160

AN:

188

Other (OTH)

AF:

0.794

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.763

AC:

115990

AN:

152028

Hom.:

44883

Cov.:

AF XY:

0.764

AC XY:

56771

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.644

AC:

26696

AN:

41422

American (AMR)

AF:

0.711

AC:

10862

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.860

AC:

2985

AN:

3470

East Asian (EAS)

AF:

0.602

AC:

3099

AN:

5152

South Asian (SAS)

AF:

0.800

AC:

3854

AN:

4820

European-Finnish (FIN)

AF:

0.872

AC:

9240

AN:

10598

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.834

AC:

56670

AN:

67980

Other (OTH)

AF:

0.768

AC:

1617

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1359

2718

4077

5436

6795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.804

Hom.:

191916

Bravo

AF:

0.741

Asia WGS

AF:

0.701

AC:

2437

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.0

(source)

DANN

Benign

0.80

PhyloP100

-0.90

PromoterAI

0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over