Variant rs6694817 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000368485.8(IL6R):c.334+52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,565,550 control chromosomes in the GnomAD database, including 257,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.60 ( 27416 hom., cov: 32)

Exomes 𝑓: 0.57 ( 230373 hom. )

Consequence

IL6R
ENST00000368485.8 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.362

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=-0.83).

BP6

Variant 1-154429496-T-C is Benign according to our data. Variant chr1-154429496-T-C is described in ClinVar as [Benign]. Clinvar id is 2688500.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 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.334+52T>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.334+52T>C		intron_variant		1	NM_000565.4	ENSP00000357470	P1	P08887-1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90395

AN:

151932

Hom.:

27369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.679

Gnomad AMI

AF:

0.686

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.485

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.455

Gnomad MID

AF:

0.567

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.582

GnomAD3 exomes

AF:

0.568

AC:

126354

AN:

222604

Hom.:

36195

AF XY:

0.557

AC XY:

66575

AN XY:

119606

show subpopulations

Gnomad AFR exome

AF:

0.684

Gnomad AMR exome

AF:

0.658

Gnomad ASJ exome

AF:

0.565

Gnomad EAS exome

AF:

0.512

Gnomad SAS exome

AF:

0.465

Gnomad FIN exome

AF:

0.470

Gnomad NFE exome

AF:

0.574

Gnomad OTH exome

AF:

0.568

GnomAD4 exome

AF:

0.569

AC:

803967

AN:

1413500

Hom.:

230373

Cov.:

AF XY:

0.564

AC XY:

392594

AN XY:

695966

show subpopulations

Gnomad4 AFR exome

AF:

0.682

Gnomad4 AMR exome

AF:

0.658

Gnomad4 ASJ exome

AF:

0.569

Gnomad4 EAS exome

AF:

0.514

Gnomad4 SAS exome

AF:

0.462

Gnomad4 FIN exome

AF:

0.476

Gnomad4 NFE exome

AF:

0.576

Gnomad4 OTH exome

AF:

0.563

GnomAD4 genome

AF:

0.595

AC:

90500

AN:

152050

Hom.:

27416

Cov.:

AF XY:

0.586

AC XY:

43563

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.680

Gnomad4 AMR

AF:

0.655

Gnomad4 ASJ

AF:

0.582

Gnomad4 EAS

AF:

0.486

Gnomad4 SAS

AF:

0.464

Gnomad4 FIN

AF:

0.455

Gnomad4 NFE

AF:

0.570

Gnomad4 OTH

AF:

0.581

Alfa

AF:

0.540

Hom.:

5117

Bravo

AF:

0.618

Asia WGS

AF:

0.491

AC:

1709

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 92% of patients studied by a panel of primary immunodeficiencies. Number of patients: 81. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.9

DANN

Benign

0.80

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