NM_000565.4:c.*228C>G

Variant names:

• chr1-154465608-C-G
• rs7514452
• NM_000565.4:c.*228C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000565.4(IL6R):​c.*228C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL6R NM_000565.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 44 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.*228C>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.*228C>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.*443C>G		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000340589.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 422222 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 222224

African (AFR) AF: 0.00 AC: 0 AN: 11898

American (AMR) AF: 0.00 AC: 0 AN: 17698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12842

East Asian (EAS) AF: 0.00 AC: 0 AN: 28784

South Asian (SAS) AF: 0.00 AC: 0 AN: 44562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1822

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 253572

Other (OTH) AF: 0.00 AC: 0 AN: 24330

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 202562

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.46
PhyloP100		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7514452; hg19: chr1-154438084;