1-154423363-C-T

Position:

• chr1-154423363-C-T

Variant summary

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

The NM_000565.4(IL6R):​c.86-5833C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 146,750 control chromosomes in the GnomAD database, including 10,713 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 0.38 (10713 hom., cov: 24)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.86-5833C>T		intron_variant		ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.86-5833C>T		intron_variant		1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.86-5833C>T		intron_variant		1		ENSP00000340589.4
IL6R	ENST00000622330.5	c.86-5833C>T		intron_variant		1		ENSP00000477739.1
IL6R	ENST00000512471.1	c.86-5833C>T		intron_variant		4		ENSP00000423184.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 55420 AN: 146638 Hom.: 10709 Cov.: 24

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.378 AC: 55443 AN: 146750 Hom.: 10713 Cov.: 24 AF XY: 0.370 AC XY: 26334 AN XY: 71230

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.369

Alfa AF: 0.388 Hom.: 5372

Bravo AF: 0.407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.54

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: rs6684439; hg19: chr1-154395839;