rs76429508

chr9-34655632-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.88

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]

ACMG classification

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 GnomAd at 13 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL11RA	ENST00000441545.7	c.128C>T	p.Ser43Phe	missense_variant	3/13	5	NM_001142784.3	P4

Frequencies

GnomAD3 genomes AF: 0.00568 AC: 864 AN: 152134 Hom.: 13 Cov.: 32

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.: 12 AF XY: 0.00261 AC XY: 355 AN XY: 135854

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.: 21 Cov.: 32 AF XY: 0.00145 AC XY: 1058 AN XY: 727236

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.: 13 Cov.: 32 AF XY: 0.00535 AC XY: 398 AN XY: 74442

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.: 6

Bravo AF: 0.00662

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0148 AC: 65

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.00277 AC: 336

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 02, 2020	This variant is associated with the following publications: (PMID: 21741611) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 26, 2024	- -

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	T
BayesDel_noAF	Benign	-0.19
Cadd	Benign	21
Dann	Uncertain	0.99
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.14	N
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	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.41	T
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	T
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

Other links and lift over

dbSNP: rs76429508; hg19: chr9-34655629;