rs4393147

Positions:

• chr1-154441561-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.949+5451C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,926 control chromosomes in the GnomAD database, including 9,381 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 0.33 (9381 hom., cov: 32)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.949+5451C>T		intron_variant		ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.949+5451C>T		intron_variant		1	NM_000565.4	ENSP00000357470.3

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49586 AN: 151808 Hom.: 9380 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.351

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.326 AC: 49590 AN: 151926 Hom.: 9381 Cov.: 32 AF XY: 0.322 AC XY: 23888 AN XY: 74246

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.347

Alfa AF: 0.319 Hom.: 1313

Bravo AF: 0.341

Asia WGS AF: 0.294 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.4
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: rs4393147; hg19: chr1-154414037;