NM_000565.4:c.1161-1415C>T

Variant names:

• chr1-154463719-C-T
• rs4240872
• NM_000565.4:c.1161-1415C>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.1161-1415C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,094 control chromosomes in the GnomAD database, including 35,806 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 (35806 hom., cov: 32)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 45 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.1161-1415C>T		intron_variant	Intron 9 of 9	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.1161-1415C>T		intron_variant	Intron 9 of 9	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.1067-1415C>T		intron_variant	Intron 8 of 8	1		ENSP00000340589.4
IL6R	ENST00000502679.1	n.474-1415C>T		intron_variant	Intron 1 of 1	2
IL6R	ENST00000507256.1	n.359-1415C>T		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102115 AN: 151976 Hom.: 35793 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.672 AC: 102173 AN: 152094 Hom.: 35806 Cov.: 32 AF XY: 0.671 AC XY: 49855 AN XY: 74352

African (AFR) AF: 0.462 AC: 19149 AN: 41454

American (AMR) AF: 0.774 AC: 11822 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2710 AN: 3472

East Asian (EAS) AF: 0.826 AC: 4272 AN: 5170

South Asian (SAS) AF: 0.758 AC: 3658 AN: 4828

European-Finnish (FIN) AF: 0.629 AC: 6649 AN: 10578

Middle Eastern (MID) AF: 0.750 AC: 219 AN: 292

European-Non Finnish (NFE) AF: 0.757 AC: 51474 AN: 67998

Other (OTH) AF: 0.700 AC: 1477 AN: 2110

Alfa AF: 0.739 Hom.: 179086

Bravo AF: 0.678

Asia WGS AF: 0.740 AC: 2573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.38
PhyloP100		0.061
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: rs4240872; hg19: chr1-154436195;