chr9-34655632-C-T

Variant names:

• chr9-34655632-C-T
• rs76429508
• NM_001142784.3:c.128C>T

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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:5
• Conservation: PhyloP100: 1.88
• Publications: 8 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 (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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

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.128C>T	p.Ser43Phe	missense	Exon 3 of 13	NP_001136256.1	Q14626-1
	IL11RA	NR_052010.2		n.215C>T		non_coding_transcript_exon	Exon 3 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11RA	ENST00000441545.7	TSL:5 MANE Select	c.128C>T	p.Ser43Phe	missense	Exon 3 of 13	ENSP00000394391.3	Q14626-1
	IL11RA	ENST00000318041.13	TSL:1	c.128C>T	p.Ser43Phe	missense	Exon 3 of 13	ENSP00000326500.8	Q14626-1
	IL11RA	ENST00000602473.5	TSL:1	c.128C>T	p.Ser43Phe	missense	Exon 2 of 10	ENSP00000473647.1	Q14626-2

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

GnomAD2 exomes AF: 0.00296 AC: 745 AN: 251378 AF XY: 0.00261

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 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

African (AFR) AF: 0.0168 AC: 563 AN: 33480

American (AMR) AF: 0.00241 AC: 108 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 850 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5762

European-Non Finnish (NFE) AF: 0.000410 AC: 456 AN: 1111998

Other (OTH) AF: 0.00391 AC: 236 AN: 60396

GnomAD4 genome AF: 0.00571 AC: 869 AN: 152252 Hom.: 13 Cov.: 32 AF XY: 0.00535 AC XY: 398 AN XY: 74442

African (AFR) AF: 0.0151 AC: 629 AN: 41546

American (AMR) AF: 0.00379 AC: 58 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68018

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00359 Hom.: 11

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.16
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.76	P
Vest4		0.44
MVP		0.64
MPC		0.29
ClinPred		0.011	T
GERP RS		5.1
PromoterAI		0.027	Neutral
Varity_R		0.48
gMVP		0.45
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

dbSNP: rs76429508; hg19: chr9-34655629;