dbSNP rs4845374: IL6R:c.1067-17T>A (chr1-154454471-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000565.4(IL6R):c.1067-17T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,294,146 control chromosomes in the GnomAD database, including 19,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2621 hom., cov: 31)

Exomes 𝑓: 0.19 ( 16526 hom. )

Consequence

IL6R
NM_000565.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.62

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-154454471-T-A is Benign according to our data. Variant chr1-154454471-T-A is described in ClinVar as [Benign]. Clinvar id is 1165317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4 link	c.1067-17T>A		intron_variant	Intron 8 of 9	ENST00000368485.8	NP_000556.1	P08887-1A0N0L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8 link	c.1067-17T>A		intron_variant	Intron 8 of 9	1	NM_000565.4	ENSP00000357470.3		P08887-1

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27232

AN:

150300

Hom.:

2614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.179

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.189

AC:

36479

AN:

192926

Hom.:

2752

AF XY:

0.188

AC XY:

19548

AN XY:

103772

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.199

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.188

AC:

215211

AN:

1143738

Hom.:

16526

Cov.:

AF XY:

0.186

AC XY:

107445

AN XY:

576474

show subpopulations

Gnomad4 AFR exome

AF:

0.280

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.192

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.193

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.181

AC:

27266

AN:

150408

Hom.:

2621

Cov.:

AF XY:

0.178

AC XY:

13082

AN XY:

73406

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.186

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.174

Hom.:

287

Bravo

AF:

0.180

Asia WGS

AF:

0.173

AC:

603

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.30

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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