chr1-154447416-G-A

Variant names:

• chr1-154447416-G-A
• rs12730935
• NM_000565.4:c.950-709G>A

Variant summary

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

The NM_000565.4(IL6R):​c.950-709G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.28 (5191 hom., cov: 15)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 25 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.950-709G>A		intron_variant	Intron 6 of 9	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.950-709G>A		intron_variant	Intron 6 of 9	1	NM_000565.4	ENSP00000357470.3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 28707 AN: 103118 Hom.: 5192 Cov.: 15

Gnomad AFR AF: 0.0976

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.278 AC: 28697 AN: 103160 Hom.: 5191 Cov.: 15 AF XY: 0.271 AC XY: 12963 AN XY: 47922

African (AFR) AF: 0.0973 AC: 2683 AN: 27562

American (AMR) AF: 0.444 AC: 3687 AN: 8296

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 942 AN: 2626

East Asian (EAS) AF: 0.290 AC: 966 AN: 3326

South Asian (SAS) AF: 0.224 AC: 689 AN: 3082

European-Finnish (FIN) AF: 0.213 AC: 939 AN: 4400

Middle Eastern (MID) AF: 0.422 AC: 70 AN: 166

European-Non Finnish (NFE) AF: 0.349 AC: 18029 AN: 51652

Other (OTH) AF: 0.303 AC: 420 AN: 1388

Alfa AF: 0.0159 Hom.: 58

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.84
DANN	Benign	0.48
PhyloP100		-0.28
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: rs12730935; hg19: chr1-154419892; COSMIC: COSV59818981;