rs10471960

Positions:

• chr5-55940546-A-G

Variant summary

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

The NM_002184.4(IL6ST):​c.*536T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 214,212 control chromosomes in the GnomAD database, including 5,855 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 0.21 (5096 hom., cov: 32)
  • Exomes 𝑓: 0.13 (759 hom.)
• Consequence: IL6ST NM_002184.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669

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]

ENSG00000262211 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6ST	NM_002184.4	c.*536T>C		3_prime_UTR_variant	17/17	ENST00000381298.7	NP_002175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6ST	ENST00000381298	c.*536T>C		3_prime_UTR_variant	17/17	1	NM_002184.4	ENSP00000370698.2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31968 AN: 151996 Hom.: 5075 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.134 AC: 8335 AN: 62100 Hom.: 759 Cov.: 0 AF XY: 0.129 AC XY: 3736 AN XY: 28880

Gnomad4 AFR exome AF: 0.445

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.0404

Gnomad4 SAS exome AF: 0.0530

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.211 AC: 32039 AN: 152112 Hom.: 5096 Cov.: 32 AF XY: 0.205 AC XY: 15231 AN XY: 74364

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0328

Gnomad4 SAS AF: 0.0707

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.190

Alfa AF: 0.136 Hom.: 1697

Bravo AF: 0.223

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.37

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: rs10471960; hg19: chr5-55236374;