rs766474176

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000565.4(IL6R):​c.106A>C​(p.Thr36Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,054 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T36A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

IL6R
NM_000565.4 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.565
Variant links:
Genes affected
IL6R (HGNC:6019): (interleukin 6 receptor) This gene encodes a subunit of the interleukin 6 (IL6) receptor complex. Interleukin 6 is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in the immune response. The IL6 receptor is a protein complex consisting of this protein and interleukin 6 signal transducer (IL6ST/GP130/IL6-beta), a receptor subunit also shared by many other cytokines. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer. Alternatively spliced transcript variants encoding distinct isoforms have been identified in this gene. A pseudogene of this gene is found on chromosome 9. [provided by RefSeq, Aug 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL6RNM_000565.4 linkc.106A>C p.Thr36Pro missense_variant Exon 2 of 10 ENST00000368485.8 NP_000556.1 P08887-1A0N0L5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL6RENST00000368485.8 linkc.106A>C p.Thr36Pro missense_variant Exon 2 of 10 1 NM_000565.4 ENSP00000357470.3 P08887-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461054
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
726660
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.44
.;T;.;T
Eigen
Benign
-0.066
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.66
T;T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Uncertain
0.47
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
.;L;L;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.8
.;D;D;D
REVEL
Benign
0.19
Sift
Benign
0.037
.;D;D;T
Sift4G
Uncertain
0.0060
D;D;D;D
Polyphen
0.93, 0.99
.;P;D;.
Vest4
0.37
MutPred
0.64
Gain of disorder (P = 0.0369);Gain of disorder (P = 0.0369);Gain of disorder (P = 0.0369);Gain of disorder (P = 0.0369);
MVP
0.62
MPC
0.88
ClinPred
0.86
D
GERP RS
3.7
Varity_R
0.65
gMVP
0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-154401692; API