Variant rs7521458 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.807+81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,375,794 control chromosomes in the GnomAD database, including 109,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.33 ( 9392 hom., cov: 32)

Exomes 𝑓: 0.40 ( 100581 hom. )

Consequence

IL6R
NM_000565.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.43

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-154435237-T-C is Benign according to our data. Variant chr1-154435237-T-C is described in ClinVar as [Benign]. Clinvar id is 2688005.Status of the report is criteria_provided_single_submitter, 1 stars.

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	Protein	UniProt
IL6R	NM_000565.4 linkuse as main transcript	c.807+81T>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.807+81T>C		intron_variant		1	NM_000565.4	ENSP00000357470	P1	P08887-1

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49648

AN:

151974

Hom.:

9391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.522

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.386

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.402

Gnomad OTH

AF:

0.351

GnomAD4 exome

AF:

0.400

AC:

489137

AN:

1223702

Hom.:

100581

AF XY:

0.397

AC XY:

242170

AN XY:

610166

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.551

Gnomad4 ASJ exome

AF:

0.393

Gnomad4 EAS exome

AF:

0.404

Gnomad4 SAS exome

AF:

0.314

Gnomad4 FIN exome

AF:

0.304

Gnomad4 NFE exome

AF:

0.415

Gnomad4 OTH exome

AF:

0.378

GnomAD4 genome

AF:

0.326

AC:

49649

AN:

152092

Hom.:

9392

Cov.:

AF XY:

0.322

AC XY:

23930

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.495

Gnomad4 ASJ

AF:

0.386

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.402

Gnomad4 OTH

AF:

0.347

Alfa

AF:

0.219

Hom.:

533

Bravo

AF:

0.341

Asia WGS

AF:

0.306

AC:

1067

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 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.14

DANN

Benign

0.14

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

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