NM_000565.4:c.-208G>C

Variant names:

• chr1-154405422-G-C
• rs4845617
• NM_000565.4:c.-208G>C

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.-208G>C variant causes a 5 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL6R NM_000565.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.652
• Publications: 54 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-AS1 (HGNC:53716): (IL6R antisense RNA 1)

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=-0.8).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6R	NM_000565.4	MANE Select	c.-208G>C		5_prime_UTR	Exon 1 of 10	NP_000556.1	P08887-1
	IL6R	NM_001382769.1		c.-208G>C		5_prime_UTR	Exon 1 of 11	NP_001369698.1
	IL6R	NM_001382770.1		c.-208G>C		5_prime_UTR	Exon 1 of 11	NP_001369699.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6R	ENST00000368485.8	TSL:1 MANE Select	c.-208G>C		5_prime_UTR	Exon 1 of 10	ENSP00000357470.3	P08887-1
	IL6R	ENST00000344086.8	TSL:1	c.-208G>C		5_prime_UTR	Exon 1 of 9	ENSP00000340589.4	P08887-2
	IL6R	ENST00000622330.5	TSL:1	c.-208G>C		5_prime_UTR	Exon 1 of 7	ENSP00000477739.1	A0A087WTB5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 381790 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 202692

African (AFR) AF: 0.00 AC: 0 AN: 7432

American (AMR) AF: 0.00 AC: 0 AN: 9978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11340

East Asian (EAS) AF: 0.00 AC: 0 AN: 23920

South Asian (SAS) AF: 0.00 AC: 0 AN: 37614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1734

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 238486

Other (OTH) AF: 0.00 AC: 0 AN: 22456

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 14362

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		0.65
PromoterAI		0.13	Neutral

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: rs4845617; hg19: chr1-154377898;