rs6698040

Variant names:

• chr1-154460472-T-C
• rs6698040
• NM_000565.4:c.1161-4662T>C

Variant summary

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

The NM_000565.4(IL6R):​c.1161-4662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,896 control chromosomes in the GnomAD database, including 35,813 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 0.67 (35813 hom., cov: 32)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 11 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 (EAS) allele frequency at 95% confidence interval = 0.805 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.1161-4662T>C		intron	N/A	NP_000556.1	P08887-1
	IL6R	NM_001382769.1		c.1260-4662T>C		intron	N/A	NP_001369698.1
	IL6R	NM_001382770.1		c.1254-4662T>C		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.1161-4662T>C		intron	N/A	ENSP00000357470.3	P08887-1
	IL6R	ENST00000344086.8	TSL:1	c.1067-4662T>C		intron	N/A	ENSP00000340589.4	P08887-2
	IL6R	ENST00000858510.1		c.1353-4662T>C		intron	N/A	ENSP00000528569.1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102105 AN: 151776 Hom.: 35796 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.673 AC: 102171 AN: 151896 Hom.: 35813 Cov.: 32 AF XY: 0.671 AC XY: 49813 AN XY: 74198

African (AFR) AF: 0.465 AC: 19252 AN: 41432

American (AMR) AF: 0.774 AC: 11791 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2715 AN: 3470

East Asian (EAS) AF: 0.826 AC: 4268 AN: 5168

South Asian (SAS) AF: 0.758 AC: 3650 AN: 4814

European-Finnish (FIN) AF: 0.629 AC: 6613 AN: 10520

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51440 AN: 67936

Other (OTH) AF: 0.701 AC: 1481 AN: 2112

Alfa AF: 0.720 Hom.: 16595

Bravo AF: 0.679

Asia WGS AF: 0.741 AC: 2577 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	0.11
DANN	Benign	0.71
PhyloP100		-1.2
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: rs6698040; hg19: chr1-154432948;