chr1-154428323-T-C

Variant names:

• chr1-154428323-T-C
• rs6427658
• NM_000565.4:c.86-873T>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.86-873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,858 control chromosomes in the GnomAD database, including 25,096 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 0.57 (25096 hom., cov: 31)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 26 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.86-873T>C		intron_variant	Intron 1 of 9	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.86-873T>C		intron_variant	Intron 1 of 9	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.86-873T>C		intron_variant	Intron 1 of 8	1		ENSP00000340589.4
IL6R	ENST00000622330.5	c.86-873T>C		intron_variant	Intron 1 of 6	1		ENSP00000477739.1
IL6R	ENST00000512471.1	c.86-873T>C		intron_variant	Intron 1 of 3	4		ENSP00000423184.1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86733 AN: 151740 Hom.: 25060 Cov.: 31

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.572 AC: 86825 AN: 151858 Hom.: 25096 Cov.: 31 AF XY: 0.563 AC XY: 41789 AN XY: 74196

African (AFR) AF: 0.600 AC: 24832 AN: 41404

American (AMR) AF: 0.644 AC: 9832 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2023 AN: 3466

East Asian (EAS) AF: 0.487 AC: 2505 AN: 5144

South Asian (SAS) AF: 0.462 AC: 2223 AN: 4808

European-Finnish (FIN) AF: 0.453 AC: 4783 AN: 10550

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38665 AN: 67906

Other (OTH) AF: 0.557 AC: 1174 AN: 2108

Alfa AF: 0.572 Hom.: 12975

Bravo AF: 0.593

Asia WGS AF: 0.483 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.054
DANN	Benign	0.49
PhyloP100		-1.6
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: rs6427658; hg19: chr1-154400799;