1-154428323-T-C

Position:

• chr1-154428323-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.86-873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,858 control chromosomes in the GnomAD database, including 25,096 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 0.57 (25096 hom., cov: 31)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6R	NM_000565.4	c.86-873T>C		intron_variant		ENST00000368485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6R	ENST00000368485.8	c.86-873T>C		intron_variant		1	NM_000565.4	P1
IL6R	ENST00000344086.8	c.86-873T>C		intron_variant		1
IL6R	ENST00000622330.5	c.86-873T>C		intron_variant		1
IL6R	ENST00000512471.1	c.86-873T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86733 AN: 151740 Hom.: 25060 Cov.: 31

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.558

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.572 AC: 86825 AN: 151858 Hom.: 25096 Cov.: 31 AF XY: 0.563 AC XY: 41789 AN XY: 74196

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.557

Alfa AF: 0.571 Hom.: 6636

Bravo AF: 0.593

Asia WGS AF: 0.483 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.054
DANN	Benign	0.49

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: rs6427658; hg19: chr1-154400799;