1-154465608-C-T

Position:

• chr1-154465608-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

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 (AMR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.*228C>T		3_prime_UTR_variant	10/10	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.*228C>T		3_prime_UTR_variant	10/10	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.*443C>T		3_prime_UTR_variant	9/9	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

Gnomad4 AFR exome AF: 0.797

Gnomad4 AMR exome AF: 0.836

Gnomad4 ASJ exome AF: 0.823

Gnomad4 EAS exome AF: 0.825

Gnomad4 SAS exome AF: 0.774

Gnomad4 FIN exome AF: 0.686

Gnomad4 NFE exome AF: 0.805

Gnomad4 OTH exome AF: 0.798

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

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.809

Alfa AF: 0.808 Hom.: 97475

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7514452; hg19: chr1-154438084; COSMIC: COSV59819711; COSMIC: COSV59819711;