rs10471960

Variant names:

• chr5-55940546-A-G
• rs10471960
• NM_002184.4:c.*536T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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)

ENSG00000262211 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL6ST	NM_002184.4	c.*536T>C		3_prime_UTR_variant	Exon 17 of 17	ENST00000381298.7	NP_002175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6ST	ENST00000381298.7	c.*536T>C		3_prime_UTR_variant	Exon 17 of 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

African (AFR) AF: 0.445 AC: 1266 AN: 2844

American (AMR) AF: 0.136 AC: 274 AN: 2012

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 510 AN: 3846

East Asian (EAS) AF: 0.0404 AC: 372 AN: 9198

South Asian (SAS) AF: 0.0530 AC: 30 AN: 566

European-Finnish (FIN) AF: 0.100 AC: 5 AN: 50

Middle Eastern (MID) AF: 0.130 AC: 50 AN: 386

European-Non Finnish (NFE) AF: 0.130 AC: 4948 AN: 38070

Other (OTH) AF: 0.172 AC: 880 AN: 5128

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

African (AFR) AF: 0.446 AC: 18498 AN: 41470

American (AMR) AF: 0.137 AC: 2091 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3472

East Asian (EAS) AF: 0.0328 AC: 170 AN: 5176

South Asian (SAS) AF: 0.0707 AC: 341 AN: 4824

European-Finnish (FIN) AF: 0.135 AC: 1429 AN: 10582

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8392 AN: 67998

Other (OTH) AF: 0.190 AC: 402 AN: 2116

Alfa AF: 0.152 Hom.: 7365

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
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10471960; hg19: chr5-55236374;