Variant rs2228044 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002184.4(IL6ST):c.442G>T(p.Gly148Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. G148R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IL6ST
NM_002184.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.73

Variant links:

Genes affected

IL6ST (HGNC:6021): (interleukin 6 cytokine family signal transducer) The protein encoded by this gene is a signal transducer shared by many cytokines, including interleukin 6 (IL6), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M (OSM). This protein functions as a part of the cytokine receptor complex. The activation of this protein is dependent upon the binding of cytokines to their receptors. vIL6, a protein related to IL6 and encoded by the Kaposi sarcoma-associated herpesvirus, can bypass the interleukin 6 receptor (IL6R) and directly activate this protein. Knockout studies in mice suggest that this gene plays a critical role in regulating myocyte apoptosis. Alternatively spliced transcript variants have been described. A related pseudogene has been identified on chromosome 17. [provided by RefSeq, May 2014]

IL6ST links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14086324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6ST	NM_002184.4 linkuse as main transcript	c.442G>T	p.Gly148Cys	missense_variant	5/17	ENST00000381298.7	NP_002175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6ST	ENST00000381298.7 linkuse as main transcript	c.442G>T	p.Gly148Cys	missense_variant	5/17	1	NM_002184.4	ENSP00000370698	P1	P40189-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449262

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720884

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:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

T;T;.;T;.;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.042

.;T;T;.;T;.

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.14

T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.0

N;N;N;N;N;N

MutationTaster

Benign

1.0

D;D;D;N;N;N;N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.90

N;N;N;.;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0040

D;D;D;.;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D;D

Polyphen

0.37

B;B;B;B;.;B

Vest4

0.19

MutPred

0.46

Loss of disorder (P = 0.0351);Loss of disorder (P = 0.0351);Loss of disorder (P = 0.0351);Loss of disorder (P = 0.0351);Loss of disorder (P = 0.0351);Loss of disorder (P = 0.0351);

MVP

0.40

MPC

0.23

ClinPred

0.72

GERP RS

5.8

Varity_R

0.51

gMVP

0.67

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over