1-154465608-C-T

Variant names:

• chr1-154465608-C-T
• rs7514452
• NM_000565.4:c.*228C>T

Variant summary

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

The NM_000565.4(IL6R):​c.*228C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 573,846 control chromosomes in the GnomAD database, including 182,452 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 0.79 (48186 hom., cov: 31)
  • Exomes 𝑓: 0.80 (134266 hom.)
• Consequence: IL6R NM_000565.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 44 publications found

Genes affected

IL6R (HGNC:6019): (interleukin 6 receptor) This gene encodes a subunit of the interleukin 6 (IL6) receptor complex. Interleukin 6 is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in the immune response. The IL6 receptor is a protein complex consisting of this protein and interleukin 6 signal transducer (IL6ST/GP130/IL6-beta), a receptor subunit also shared by many other cytokines. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer. Alternatively spliced transcript variants encoding distinct isoforms have been identified in this gene. A pseudogene of this gene is found on chromosome 9. [provided by RefSeq, Aug 2020]

IL6R Gene-Disease associations (from GenCC):

• hyper-IgE recurrent infection syndrome 5, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.*228C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.*228C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.*443C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000340589.4

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120728 AN: 151948 Hom.: 48133 Cov.: 31

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.808

GnomAD4 exome AF: 0.797 AC: 336075 AN: 421780 Hom.: 134266 Cov.: 4 AF XY: 0.795 AC XY: 176440 AN XY: 221998

African (AFR) AF: 0.797 AC: 9471 AN: 11878

American (AMR) AF: 0.836 AC: 14787 AN: 17688

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 10562 AN: 12830

East Asian (EAS) AF: 0.825 AC: 23700 AN: 28742

South Asian (SAS) AF: 0.774 AC: 34473 AN: 44540

European-Finnish (FIN) AF: 0.686 AC: 18310 AN: 26672

Middle Eastern (MID) AF: 0.805 AC: 1466 AN: 1822

European-Non Finnish (NFE) AF: 0.805 AC: 203914 AN: 253306

Other (OTH) AF: 0.798 AC: 19392 AN: 24302

GnomAD4 genome AF: 0.795 AC: 120839 AN: 152066 Hom.: 48186 Cov.: 31 AF XY: 0.788 AC XY: 58588 AN XY: 74314

African (AFR) AF: 0.791 AC: 32831 AN: 41496

American (AMR) AF: 0.839 AC: 12817 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2860 AN: 3472

East Asian (EAS) AF: 0.822 AC: 4239 AN: 5154

South Asian (SAS) AF: 0.770 AC: 3713 AN: 4820

European-Finnish (FIN) AF: 0.665 AC: 7027 AN: 10568

Middle Eastern (MID) AF: 0.825 AC: 241 AN: 292

European-Non Finnish (NFE) AF: 0.803 AC: 54610 AN: 67976

Other (OTH) AF: 0.809 AC: 1705 AN: 2108

Alfa AF: 0.806 Hom.: 202562

Bravo AF: 0.811

Asia WGS AF: 0.775 AC: 2696 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	0.12
DANN	Benign	0.38
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7514452; hg19: chr1-154438084; COSMIC: COSV59819711; COSMIC: COSV59819711;