dbSNP rs11744523: IL6ST:c.-16+2636A>T (chr5-55980088-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002184.4(IL6ST):c.-16+2636A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 152,268 control chromosomes in the GnomAD database, including 674 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.088 ( 674 hom., cov: 32)

Consequence

IL6ST
NM_002184.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.284

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

hyper-IgE recurrent infection syndrome 4A, autosomal dominant
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hyper-IgE recurrent infection syndrome 4, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

IL6ST links:

ENSG00000249236 (HGNC:):

ENSG00000249236 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6ST	NM_002184.4 link	c.-16+2636A>T		intron_variant	Intron 2 of 16	ENST00000381298.7	NP_002175.2	P40189-1Q17RA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6ST	ENST00000381298.7 link	c.-16+2636A>T		intron_variant	Intron 2 of 16	1	NM_002184.4	ENSP00000370698.2		P40189-1

Frequencies

GnomAD3 genomes

AF:

0.0885

AC:

13461

AN:

152150

Hom.:

675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0582

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.0776

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0273

Gnomad FIN

AF:

0.0948

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.0960

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0884

AC:

13460

AN:

152268

Hom.:

674

Cov.:

AF XY:

0.0841

AC XY:

6264

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0582

AC:

2418

AN:

41550

American (AMR)

AF:

0.0775

AC:

1185

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

444

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5186

South Asian (SAS)

AF:

0.0269

AC:

130

AN:

4830

European-Finnish (FIN)

AF:

0.0948

AC:

1005

AN:

10600

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.115

AC:

7818

AN:

68012

Other (OTH)

AF:

0.0950

AC:

201

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

647

1294

1941

2588

3235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.100

Hom.:

112

Bravo

AF:

0.0882

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.90

(source)

DANN

Benign

0.20

PhyloP100

0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over