1-154453621-A-G

Variant names:

• chr1-154453621-A-G
• rs6689393
• NM_000565.4:c.1067-867A>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.1067-867A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,106 control chromosomes in the GnomAD database, including 28,054 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 0.60 (28054 hom., cov: 33)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 27 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 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.1067-867A>G		intron	N/A	NP_000556.1	P08887-1
	IL6R	NM_001382769.1		c.1067-452A>G		intron	N/A	NP_001369698.1
	IL6R	NM_001382770.1		c.1160-867A>G		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.1067-867A>G		intron	N/A	ENSP00000357470.3	P08887-1
	IL6R	ENST00000344086.8	TSL:1	c.1066+3641A>G		intron	N/A	ENSP00000340589.4	P08887-2
	IL6R	ENST00000858510.1		c.1160-452A>G		intron	N/A	ENSP00000528569.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91207 AN: 151988 Hom.: 28010 Cov.: 33

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.600 AC: 91309 AN: 152106 Hom.: 28054 Cov.: 33 AF XY: 0.591 AC XY: 43921 AN XY: 74360

African (AFR) AF: 0.705 AC: 29267 AN: 41514

American (AMR) AF: 0.654 AC: 9977 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2096 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2405 AN: 5170

South Asian (SAS) AF: 0.471 AC: 2274 AN: 4828

European-Finnish (FIN) AF: 0.445 AC: 4705 AN: 10578

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38577 AN: 67974

Other (OTH) AF: 0.584 AC: 1229 AN: 2104

Alfa AF: 0.590 Hom.: 5566

Bravo AF: 0.624

Asia WGS AF: 0.484 AC: 1687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.056
DANN	Benign	0.24
PhyloP100		-2.4
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: rs6689393; hg19: chr1-154426097;