rs7518199

chr1-154434943-A-Cchr1-154434943-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000565.4(IL6R):c.641-47A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,597,692 control chromosomes in the GnomAD database, including 128,677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (10131 hom., cov: 30)
  • Exomes 𝑓: 0.40 (118546 hom.)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0310

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-154434943-A-C is Benign according to our data. Variant chr1-154434943-A-C is described in ClinVar as [Benign]. Clinvar id is 2688545.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6R	NM_000565.4	c.641-47A>C		intron_variant		ENST00000368485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6R	ENST00000368485.8	c.641-47A>C		intron_variant		1	NM_000565.4	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53348 AN: 151652 Hom.: 10128 Cov.: 30

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.375

GnomAD3 exomes AF: 0.394 AC: 94493 AN: 240104 Hom.: 19450 AF XY: 0.388 AC XY: 50500 AN XY: 130134

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.562

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.394

Gnomad SAS exome AF: 0.314

Gnomad FIN exome AF: 0.298

Gnomad NFE exome AF: 0.405

Gnomad OTH exome AF: 0.402

GnomAD4 exome AF: 0.401 AC: 579609 AN: 1445920 Hom.: 118546 Cov.: 29 AF XY: 0.398 AC XY: 285960 AN XY: 719104

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.315

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.413

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.352 AC: 53370 AN: 151772 Hom.: 10131 Cov.: 30 AF XY: 0.347 AC XY: 25714 AN XY: 74166

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.371

Alfa AF: 0.396 Hom.: 13072

Bravo AF: 0.369

Asia WGS AF: 0.301 AC: 1047 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 82% of patients studied by a panel of primary immunodeficiencies. Number of patients: 72. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.3
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7518199; hg19: chr1-154407419;