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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen, PanelApp Australia, Orphanet

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL11RA	NM_001142784.3 link	c.-1+100A>G		intron_variant	Intron 1 of 12	ENST00000441545.7	NP_001136256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL11RA	ENST00000441545.7 link	c.-1+100A>G		intron_variant	Intron 1 of 12	5	NM_001142784.3	ENSP00000394391.3
ENSG00000258728	ENST00000556278.1 link	c.433-2885A>G		intron_variant	Intron 4 of 7	5		ENSP00000451792.1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over