Variant rs7518199 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0310

Variant links:

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]

IL6R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
IL6R	NM_000565.4 linkuse as main transcript	c.641-47A>C		intron_variant		ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8 linkuse as main transcript	c.641-47A>C		intron_variant		1	NM_000565.4	ENSP00000357470	P1	P08887-1

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53348

AN:

151652

Hom.:

10128

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.398

AC XY:

285960

AN XY:

719104

show subpopulations

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.:

AF XY:

0.347

AC XY:

25714

AN XY:

74166

show subpopulations

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over