chr1-154466404-T-C

Variant names:

• chr1-154466404-T-C
• rs4072391
• NM_000565.4:c.*1024T>C

Variant summary

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

The NM_001382769.1(IL6R):​c.*1024T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,182 control chromosomes in the GnomAD database, including 44,763 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 0.76 (44762 hom., cov: 32)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: IL6R NM_001382769.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734
• Publications: 38 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382769.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6R	NM_000565.4	MANE Select	c.*1024T>C		3_prime_UTR	Exon 10 of 10	NP_000556.1
	IL6R	NM_001382769.1		c.*1024T>C		3_prime_UTR	Exon 11 of 11	NP_001369698.1
	IL6R	NM_001382770.1		c.*1024T>C		3_prime_UTR	Exon 11 of 11	NP_001369699.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6R	ENST00000368485.8	TSL:1 MANE Select	c.*1024T>C		3_prime_UTR	Exon 10 of 10	ENSP00000357470.3
	IL6R	ENST00000344086.8	TSL:1	c.*1239T>C		3_prime_UTR	Exon 9 of 9	ENSP00000340589.4
	IL6R	ENST00000858510.1		c.*1024T>C		3_prime_UTR	Exon 12 of 12	ENSP00000528569.1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116176 AN: 152060 Hom.: 44726 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.789

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.764 AC: 116266 AN: 152178 Hom.: 44762 Cov.: 32 AF XY: 0.758 AC XY: 56403 AN XY: 74382

African (AFR) AF: 0.685 AC: 28413 AN: 41500

American (AMR) AF: 0.828 AC: 12655 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2866 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4248 AN: 5178

South Asian (SAS) AF: 0.769 AC: 3706 AN: 4822

European-Finnish (FIN) AF: 0.664 AC: 7029 AN: 10582

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54640 AN: 68020

Other (OTH) AF: 0.790 AC: 1672 AN: 2116

Alfa AF: 0.800 Hom.: 63060

Bravo AF: 0.775

Asia WGS AF: 0.767 AC: 2670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.48
DANN	Benign	0.47
PhyloP100		-0.73
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: rs4072391; hg19: chr1-154438880;