rs4379670

Positions:

• chr1-154467389-T-A
• chr1-154467389-T-C
• chr1-154467389-T-G

Variant summary

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

The NM_000565.4(IL6R):​c.*2009T>A 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 152,100 control chromosomes in the GnomAD database, including 48,301 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 0.80 (48296 hom., cov: 31)
  • Exomes 𝑓: 0.71 (5 hom.)
• Consequence: IL6R NM_000565.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6R	NM_000565.4	c.*2009T>A		3_prime_UTR_variant	10/10	ENST00000368485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6R	ENST00000368485.8	c.*2009T>A		3_prime_UTR_variant	10/10	1	NM_000565.4	P1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120883 AN: 151968 Hom.: 48243 Cov.: 31

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.828

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.808

GnomAD4 exome AF: 0.714 AC: 10 AN: 14 Hom.: 5 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.796 AC: 120994 AN: 152086 Hom.: 48296 Cov.: 31 AF XY: 0.790 AC XY: 58678 AN XY: 74322

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.809

Alfa AF: 0.789 Hom.: 5842

Bravo AF: 0.811

Asia WGS AF: 0.772 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.65

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: rs4379670; hg19: chr1-154439865;