1-154467389-T-A

Variant names:

• chr1-154467389-T-A
• rs4379670
• NM_000565.4:c.*2009T>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.*2009T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,100 control chromosomes in the GnomAD database, including 48,301 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 0.80 (48296 hom., cov: 31)
  • Exomes 𝑓: 0.71 (5 hom.)
• Consequence: IL6R NM_000565.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 23 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000565.4. 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.*2009T>A		3_prime_UTR	Exon 10 of 10	NP_000556.1
	IL6R	NM_001382769.1		c.*2009T>A		3_prime_UTR	Exon 11 of 11	NP_001369698.1
	IL6R	NM_001382770.1		c.*2009T>A		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.*2009T>A		3_prime_UTR	Exon 10 of 10	ENSP00000357470.3

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120883 AN: 151968 Hom.: 48243 Cov.: 31

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.828

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.808

GnomAD4 exome AF: 0.714 AC: 10 AN: 14 Hom.: 5 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 8 AN: 12

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.796 AC: 120994 AN: 152086 Hom.: 48296 Cov.: 31 AF XY: 0.790 AC XY: 58678 AN XY: 74322

African (AFR) AF: 0.792 AC: 32832 AN: 41476

American (AMR) AF: 0.840 AC: 12834 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2866 AN: 3470

East Asian (EAS) AF: 0.821 AC: 4255 AN: 5180

South Asian (SAS) AF: 0.768 AC: 3701 AN: 4818

European-Finnish (FIN) AF: 0.667 AC: 7044 AN: 10558

Middle Eastern (MID) AF: 0.829 AC: 242 AN: 292

European-Non Finnish (NFE) AF: 0.805 AC: 54716 AN: 67994

Other (OTH) AF: 0.809 AC: 1708 AN: 2112

Alfa AF: 0.789 Hom.: 5842

Bravo AF: 0.811

Asia WGS AF: 0.772 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.65
PhyloP100		-1.0
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: rs4379670; hg19: chr1-154439865;