5-55941186-C-T

Position:

chr5-55941186-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002184.4(IL6ST):c.2653G>A(p.Val885Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 1,614,144 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 31 hom. )

Consequence

IL6ST
NM_002184.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0390

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002128154).

BP6

Variant 5-55941186-C-T is Benign according to our data. Variant chr5-55941186-C-T is described in ClinVar as [Benign]. Clinvar id is 774177.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00341 (4991/1461826) while in subpopulation SAS AF= 0.0179 (1547/86254). AF 95% confidence interval is 0.0172. There are 31 homozygotes in gnomad4_exome. There are 2849 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6ST	NM_002184.4 linkuse as main transcript	c.2653G>A	p.Val885Ile	missense_variant	17/17	ENST00000381298.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6ST	ENST00000381298.7 linkuse as main transcript	c.2653G>A	p.Val885Ile	missense_variant	17/17	1	NM_002184.4	P1	P40189-1
	ENST00000576302.1 linkuse as main transcript	n.268-12C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00229

AC:

349

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0159

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00382

AC:

959

AN:

251364

Hom.:

AF XY:

0.00462

AC XY:

627

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0177

Gnomad FIN exome

AF:

0.00407

Gnomad NFE exome

AF:

0.00258

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00341

AC:

4991

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

2849

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0179

Gnomad4 FIN exome

AF:

0.00382

Gnomad4 NFE exome

AF:

0.00268

Gnomad4 OTH exome

AF:

0.00318

GnomAD4 genome

AF:

0.00229

AC:

349

AN:

152318

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0159

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00273

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00233

Hom.:

Bravo

AF:

0.00167

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00393

AC:

477

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00249

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

IL6ST-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.7

DANN

Benign

0.54

DEOGEN2

Benign

0.097

T;T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.64

.;T;.;T

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;L;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.13

N;N;.;N

REVEL

Benign

0.012

Sift

Benign

0.54

T;T;.;T

Sift4G

Benign

0.90

T;T;T;T

Polyphen

0.0010

B;B;B;.

Vest4

0.037

MVP

0.22

MPC

0.099

ClinPred

0.00030

GERP RS

-0.55

Varity_R

0.012

gMVP

0.11

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over