5-55940178-T-C

Variant names:

• chr5-55940178-T-C
• rs11574783
• NM_002184.4:c.*904A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002184.4(IL6ST):​c.*904A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 206,446 control chromosomes in the GnomAD database, including 765 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 0.087 (654 hom., cov: 32)
  • Exomes 𝑓: 0.062 (111 hom.)
• Consequence: IL6ST NM_002184.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 6 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6ST	NM_002184.4	c.*904A>G		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.*904A>G		3_prime_UTR_variant	Exon 17 of 17	1	NM_002184.4	ENSP00000370698.2

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13202 AN: 151570 Hom.: 652 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0659

Gnomad ASJ AF: 0.0707

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.0610

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0712

Gnomad OTH AF: 0.0873

GnomAD4 exome AF: 0.0622 AC: 3404 AN: 54760 Hom.: 111 Cov.: 0 AF XY: 0.0620 AC XY: 1583 AN XY: 25520

African (AFR) AF: 0.114 AC: 284 AN: 2492

American (AMR) AF: 0.0638 AC: 104 AN: 1630

Ashkenazi Jewish (ASJ) AF: 0.0650 AC: 226 AN: 3478

East Asian (EAS) AF: 0.0372 AC: 315 AN: 8478

South Asian (SAS) AF: 0.0390 AC: 18 AN: 462

European-Finnish (FIN) AF: 0.0227 AC: 1 AN: 44

Middle Eastern (MID) AF: 0.0693 AC: 23 AN: 332

European-Non Finnish (NFE) AF: 0.0636 AC: 2116 AN: 33258

Other (OTH) AF: 0.0691 AC: 317 AN: 4586

GnomAD4 genome AF: 0.0871 AC: 13212 AN: 151686 Hom.: 654 Cov.: 32 AF XY: 0.0869 AC XY: 6438 AN XY: 74102

African (AFR) AF: 0.126 AC: 5227 AN: 41350

American (AMR) AF: 0.0658 AC: 1003 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0707 AC: 245 AN: 3466

East Asian (EAS) AF: 0.0325 AC: 168 AN: 5166

South Asian (SAS) AF: 0.0604 AC: 291 AN: 4814

European-Finnish (FIN) AF: 0.115 AC: 1196 AN: 10434

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0712 AC: 4836 AN: 67910

Other (OTH) AF: 0.0869 AC: 183 AN: 2106

Alfa AF: 0.0677 Hom.: 332

Bravo AF: 0.0864

Asia WGS AF: 0.0740 AC: 256 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.96
DANN	Benign	0.48
PhyloP100		-1.2
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: rs11574783; hg19: chr5-55236006;