rs4845623

Positions:

• chr1-154443301-A-G

Variant summary

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

The NM_000565.4(IL6R):​c.950-4824A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,084 control chromosomes in the GnomAD database, including 17,389 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 0.47 (17389 hom., cov: 33)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.950-4824A>G		intron_variant		ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.950-4824A>G		intron_variant		1	NM_000565.4	ENSP00000357470	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70845 AN: 151966 Hom.: 17346 Cov.: 33

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.466 AC: 70937 AN: 152084 Hom.: 17389 Cov.: 33 AF XY: 0.457 AC XY: 33988 AN XY: 74332

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.449

Alfa AF: 0.429 Hom.: 7201

Bravo AF: 0.498

Asia WGS AF: 0.328 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.027
DANN	Benign	0.21

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: rs4845623; hg19: chr1-154415777;