1-154453788-C-T

Variant names:

• chr1-154453788-C-T
• rs4129267
• NM_000565.4:c.1067-700C>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.1067-700C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,840 control chromosomes in the GnomAD database, including 9,014 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 0.32 (9014 hom., cov: 31)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 229 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000565.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6R	NM_000565.4	MANE Select	c.1067-700C>T		intron	N/A	NP_000556.1	P08887-1
	IL6R	NM_001382769.1		c.1067-285C>T		intron	N/A	NP_001369698.1
	IL6R	NM_001382770.1		c.1160-700C>T		intron	N/A	NP_001369699.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6R	ENST00000368485.8	TSL:1 MANE Select	c.1067-700C>T		intron	N/A	ENSP00000357470.3	P08887-1
	IL6R	ENST00000344086.8	TSL:1	c.1066+3808C>T		intron	N/A	ENSP00000340589.4	P08887-2
	IL6R	ENST00000858510.1		c.1160-285C>T		intron	N/A	ENSP00000528569.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48685 AN: 151722 Hom.: 9014 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.321 AC: 48685 AN: 151840 Hom.: 9014 Cov.: 31 AF XY: 0.316 AC XY: 23445 AN XY: 74182

African (AFR) AF: 0.137 AC: 5688 AN: 41424

American (AMR) AF: 0.489 AC: 7447 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3468

East Asian (EAS) AF: 0.359 AC: 1849 AN: 5146

South Asian (SAS) AF: 0.290 AC: 1396 AN: 4812

European-Finnish (FIN) AF: 0.278 AC: 2928 AN: 10532

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26688 AN: 67902

Other (OTH) AF: 0.342 AC: 721 AN: 2108

Alfa AF: 0.376 Hom.: 38545

Bravo AF: 0.335

Asia WGS AF: 0.286 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	15
DANN	Benign	0.56
PhyloP100		1.9
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: rs4129267; hg19: chr1-154426264;