rs7529229

Positions:

• chr1-154448302-T-C
• chr1-154448302-T-G

Variant summary

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

The NM_000565.4(IL6R):​c.996+131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 708,300 control chromosomes in the GnomAD database, including 65,063 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 (18131 hom., cov: 32)
  • Exomes 𝑓: 0.40 (46932 hom.)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.996+131T>C		intron_variant		ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.996+131T>C		intron_variant		1	NM_000565.4	ENSP00000357470	P1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71759 AN: 151930 Hom.: 18086 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.403 AC: 224080 AN: 556252 Hom.: 46932 AF XY: 0.396 AC XY: 117042 AN XY: 295712

Gnomad4 AFR exome AF: 0.651

Gnomad4 AMR exome AF: 0.574

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.309

Gnomad4 FIN exome AF: 0.305

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.410

GnomAD4 genome AF: 0.473 AC: 71853 AN: 152048 Hom.: 18131 Cov.: 32 AF XY: 0.463 AC XY: 34415 AN XY: 74318

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.453

Alfa AF: 0.448 Hom.: 2676

Bravo AF: 0.506

Asia WGS AF: 0.323 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.41

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: rs7529229; hg19: chr1-154420778;