rs4341355

Positions:

• chr1-154463928-C-G

Variant summary

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

The NM_000565.4(IL6R):​c.1161-1206C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 151,950 control chromosomes in the GnomAD database, including 35,765 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 0.67 (35765 hom., cov: 30)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.1161-1206C>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.1161-1206C>G		intron_variant		1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.1067-1206C>G		intron_variant		1		ENSP00000340589.4
IL6R	ENST00000502679.1	n.474-1206C>G		intron_variant		2
IL6R	ENST00000507256.1	n.359-1206C>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102018 AN: 151832 Hom.: 35751 Cov.: 30

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.672 AC: 102077 AN: 151950 Hom.: 35765 Cov.: 30 AF XY: 0.670 AC XY: 49795 AN XY: 74268

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.700

Alfa AF: 0.694 Hom.: 4683

Bravo AF: 0.678

Asia WGS AF: 0.740 AC: 2573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.57

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: rs4341355; hg19: chr1-154436404;