rs12083537

Variant names:

• chr1-154408627-A-G
• rs12083537
• NM_000565.4:c.85+2913A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 62 publications found

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 Gene-Disease associations (from GenCC):

• hyper-IgE recurrent infection syndrome 5, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.85+2913A>G		intron_variant	Intron 1 of 9	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.85+2913A>G		intron_variant	Intron 1 of 9	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.85+2913A>G		intron_variant	Intron 1 of 8	1		ENSP00000340589.4
IL6R	ENST00000622330.5	c.85+2913A>G		intron_variant	Intron 1 of 6	1		ENSP00000477739.1
IL6R	ENST00000512471.1	c.85+2913A>G		intron_variant	Intron 1 of 3	4		ENSP00000423184.1

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

African (AFR) AF: 0.294 AC: 12169 AN: 41422

American (AMR) AF: 0.171 AC: 2608 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3466

East Asian (EAS) AF: 0.0988 AC: 510 AN: 5162

South Asian (SAS) AF: 0.152 AC: 733 AN: 4816

European-Finnish (FIN) AF: 0.220 AC: 2323 AN: 10566

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14071 AN: 67940

Other (OTH) AF: 0.180 AC: 380 AN: 2108

Alfa AF: 0.212 Hom.: 5478

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12083537; hg19: chr1-154381103;