1-154423363-C-T

Variant names:

• chr1-154423363-C-T
• rs6684439
• NM_000565.4:c.86-5833C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000565.4(IL6R):​c.86-5833C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 146,750 control chromosomes in the GnomAD database, including 10,713 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 0.38 (10713 hom., cov: 24)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 43 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.86-5833C>T		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.86-5833C>T		intron_variant	Intron 1 of 9	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.86-5833C>T		intron_variant	Intron 1 of 8	1		ENSP00000340589.4
IL6R	ENST00000622330.5	c.86-5833C>T		intron_variant	Intron 1 of 6	1		ENSP00000477739.1
IL6R	ENST00000512471.1	c.86-5833C>T		intron_variant	Intron 1 of 3	4		ENSP00000423184.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 55420 AN: 146638 Hom.: 10709 Cov.: 24

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.378 AC: 55443 AN: 146750 Hom.: 10713 Cov.: 24 AF XY: 0.370 AC XY: 26334 AN XY: 71230

African (AFR) AF: 0.348 AC: 13824 AN: 39776

American (AMR) AF: 0.502 AC: 7225 AN: 14404

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1290 AN: 3390

East Asian (EAS) AF: 0.367 AC: 1810 AN: 4934

South Asian (SAS) AF: 0.290 AC: 1338 AN: 4616

European-Finnish (FIN) AF: 0.269 AC: 2638 AN: 9804

Middle Eastern (MID) AF: 0.382 AC: 107 AN: 280

European-Non Finnish (NFE) AF: 0.391 AC: 26060 AN: 66662

Other (OTH) AF: 0.369 AC: 747 AN: 2022

Alfa AF: 0.386 Hom.: 7001

Bravo AF: 0.407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.54
PhyloP100		0.029
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: rs6684439; hg19: chr1-154395839;