1-154466404-T-C

Position:

• chr1-154466404-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000565.4(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_000565.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.*1024T>C		3_prime_UTR_variant	10/10	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.*1024T>C		3_prime_UTR_variant	10/10	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.*1239T>C		3_prime_UTR_variant	9/9	1		ENSP00000340589.4

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

Gnomad4 FIN exome AF: 1.00

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.790

Alfa AF: 0.804 Hom.: 49091

Bravo AF: 0.775

Asia WGS AF: 0.767 AC: 2670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.48
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs4072391; hg19: chr1-154438880;