rs76429508

Positions:

chr9-34655632-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001142784.3(IL11RA):c.128C>T(p.Ser43Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,614,122 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 21 hom. )

Consequence

IL11RA
NM_001142784.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.88

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046159923).

BP6

Variant 9-34655632-C-T is Benign according to our data. Variant chr9-34655632-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 402971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00571 (869/152252) while in subpopulation AFR AF= 0.0151 (629/41546). AF 95% confidence interval is 0.0142. There are 13 homozygotes in gnomad4. There are 398 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL11RA	NM_001142784.3 linkuse as main transcript	c.128C>T	p.Ser43Phe	missense_variant	3/13	ENST00000441545.7	NP_001136256.1
IL11RA	NR_052010.2 linkuse as main transcript	n.215C>T		non_coding_transcript_exon_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL11RA	ENST00000441545.7 linkuse as main transcript	c.128C>T	p.Ser43Phe	missense_variant	3/13	5	NM_001142784.3	ENSP00000394391	P4	Q14626-1

Frequencies

GnomAD3 genomes

AF:

0.00568

AC:

864

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00296

AC:

745

AN:

251378

Hom.:

AF XY:

0.00261

AC XY:

355

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0154

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.0337

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000545

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00153

AC:

2231

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

1058

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0168

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.0325

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000410

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.00571

AC:

869

AN:

152252

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

398

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0151

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.0357

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.00662

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00277

AC:

336

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 02, 2020	This variant is associated with the following publications: (PMID: 21741611) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: High allele frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

.;D;D;.;D;.;.;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.84

T;.;.;T;D;T;D;D

MetaRNN

Benign

0.0046

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

2.0

.;M;M;.;M;.;.;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.30

N;D;D;D;D;D;D;.

REVEL

Benign

0.16

Sift

Uncertain

0.014

D;D;D;D;D;D;D;.

Sift4G

Uncertain

0.0050

D;D;D;D;D;D;D;D

Polyphen

0.76

.;P;P;.;P;.;.;.

Vest4

0.44, 0.44, 0.45

MVP

0.64

MPC

0.29

ClinPred

0.011

GERP RS

5.1

Varity_R

0.48

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over