rs4845622

chr1-154438943-A-Cchr1-154438943-A-G

Variant summary

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

The NM_000565.4(IL6R):c.949+2833A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,018 control chromosomes in the GnomAD database, including 9,367 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 0.33 (9367 hom., cov: 31)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.78

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6R	NM_000565.4	c.949+2833A>C		intron_variant		ENST00000368485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6R	ENST00000368485.8	c.949+2833A>C		intron_variant		1	NM_000565.4	P1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49531 AN: 151900 Hom.: 9366 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.326 AC: 49533 AN: 152018 Hom.: 9367 Cov.: 31 AF XY: 0.321 AC XY: 23866 AN XY: 74284

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.347

Alfa AF: 0.362 Hom.: 2480

Bravo AF: 0.340

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.032
Dann	Benign	0.76

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: rs4845622; hg19: chr1-154411419;