rs12083537

Positions:

• chr1-154408627-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.85+2913A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,940 control chromosomes in the GnomAD database, including 4,020 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 0.22 (4020 hom., cov: 31)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.85+2913A>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.85+2913A>G		intron_variant		1	NM_000565.4	ENSP00000357470	P1
IL6R	ENST00000344086.8	c.85+2913A>G		intron_variant		1		ENSP00000340589
IL6R	ENST00000622330.5	c.85+2913A>G		intron_variant		1		ENSP00000477739
IL6R	ENST00000512471.1	c.85+2913A>G		intron_variant		4		ENSP00000423184

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33497 AN: 151822 Hom.: 4010 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0991

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.221 AC: 33548 AN: 151940 Hom.: 4020 Cov.: 31 AF XY: 0.219 AC XY: 16276 AN XY: 74262

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.0988

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.180

Alfa AF: 0.209 Hom.: 808

Bravo AF: 0.220

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.080
DANN	Benign	0.27

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: rs12083537; hg19: chr1-154381103;