chr1-154459566-G-C

Variant names:

• chr1-154459566-G-C
• rs10752641
• NM_000565.4:c.1160+4985G>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.1160+4985G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,102 control chromosomes in the GnomAD database, including 40,400 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 0.73 (40400 hom., cov: 32)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• Publications: 19 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.1160+4985G>C		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.1160+4985G>C		intron_variant	Intron 9 of 9	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.1067-5568G>C		intron_variant	Intron 8 of 8	1		ENSP00000340589.4
IL6R	ENST00000502679.1	n.473+4985G>C		intron_variant	Intron 1 of 1	2
IL6R	ENST00000507256.1	n.358+4985G>C		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110295 AN: 151984 Hom.: 40367 Cov.: 32

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.726 AC: 110383 AN: 152102 Hom.: 40400 Cov.: 32 AF XY: 0.721 AC XY: 53638 AN XY: 74344

African (AFR) AF: 0.650 AC: 26967 AN: 41492

American (AMR) AF: 0.791 AC: 12092 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2717 AN: 3472

East Asian (EAS) AF: 0.826 AC: 4277 AN: 5180

South Asian (SAS) AF: 0.756 AC: 3644 AN: 4822

European-Finnish (FIN) AF: 0.630 AC: 6648 AN: 10556

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51523 AN: 67982

Other (OTH) AF: 0.732 AC: 1546 AN: 2112

Alfa AF: 0.728 Hom.: 5026

Bravo AF: 0.738

Asia WGS AF: 0.751 AC: 2613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.43
PhyloP100		0.12
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: rs10752641; hg19: chr1-154432042;