rs4601580

Positions:

• chr1-154421941-T-A
• chr1-154421941-T-C

Variant summary

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

The NM_000565.4(IL6R):​c.86-7255T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 150,552 control chromosomes in the GnomAD database, including 20,906 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 0.52 (20906 hom., cov: 28)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.86-7255T>A		intron_variant		ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.86-7255T>A		intron_variant		1	NM_000565.4	ENSP00000357470	P1
IL6R	ENST00000344086.8	c.86-7255T>A		intron_variant		1		ENSP00000340589
IL6R	ENST00000622330.5	c.86-7255T>A		intron_variant		1		ENSP00000477739
IL6R	ENST00000512471.1	c.86-7255T>A		intron_variant		4		ENSP00000423184

Frequencies

GnomAD3 genomes AF: 0.524 AC: 78805 AN: 150434 Hom.: 20903 Cov.: 28

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.524 AC: 78845 AN: 150552 Hom.: 20906 Cov.: 28 AF XY: 0.523 AC XY: 38470 AN XY: 73510

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.526

Alfa AF: 0.512 Hom.: 2453

Bravo AF: 0.530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.39

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: rs4601580; hg19: chr1-154394417;