chr1-154446403-C-T

Position:

• chr1-154446403-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.950-1722C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,956 control chromosomes in the GnomAD database, including 18,007 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 0.47 (18007 hom., cov: 31)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.950-1722C>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.950-1722C>T		intron_variant		1	NM_000565.4	ENSP00000357470	P1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71466 AN: 151838 Hom.: 17959 Cov.: 31

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.471 AC: 71566 AN: 151956 Hom.: 18007 Cov.: 31 AF XY: 0.461 AC XY: 34259 AN XY: 74260

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.452

Alfa AF: 0.418 Hom.: 31991

Bravo AF: 0.504

Asia WGS AF: 0.321 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.70
DANN	Benign	0.62

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: rs4537545; hg19: chr1-154418879;