rs11741953

Positions:

• chr5-55971986-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002184.4(IL6ST):​c.65-2131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,164 control chromosomes in the GnomAD database, including 1,217 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 0.12 (1217 hom., cov: 32)
• Consequence: IL6ST NM_002184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6ST	NM_002184.4	c.65-2131A>G		intron_variant		ENST00000381298.7	NP_002175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6ST	ENST00000381298.7	c.65-2131A>G		intron_variant		1	NM_002184.4	ENSP00000370698.2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18532 AN: 152046 Hom.: 1213 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0325

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.122 AC: 18561 AN: 152164 Hom.: 1217 Cov.: 32 AF XY: 0.119 AC XY: 8848 AN XY: 74394

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0328

Gnomad4 SAS AF: 0.0698

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.125

Alfa AF: 0.119 Hom.: 2265

Bravo AF: 0.123

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs11741953; hg19: chr5-55267814;