1-154453788-C-T

Position:

• chr1-154453788-C-T

Variant summary

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

The ENST00000368485.8(IL6R):​c.1067-700C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,840 control chromosomes in the GnomAD database, including 9,014 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 0.32 (9014 hom., cov: 31)
• Consequence: IL6R ENST00000368485.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.1067-700C>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.1067-700C>T		intron_variant		1	NM_000565.4	ENSP00000357470	P1
IL6R	ENST00000344086.8	c.1066+3808C>T		intron_variant		1		ENSP00000340589
IL6R	ENST00000515190.1	c.475-700C>T		intron_variant		2		ENSP00000423036
IL6R	ENST00000507256.1	n.265-700C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48685 AN: 151722 Hom.: 9014 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.321 AC: 48685 AN: 151840 Hom.: 9014 Cov.: 31 AF XY: 0.316 AC XY: 23445 AN XY: 74182

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.342

Alfa AF: 0.389 Hom.: 26430

Bravo AF: 0.335

Asia WGS AF: 0.286 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	15
DANN	Benign	0.56

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: rs4129267; hg19: chr1-154426264;