1-154405680-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_000565.4(IL6R):c.51A>G(p.Gly17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,528,286 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 22 hom. )

Consequence

IL6R
NM_000565.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.722

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:

IL6R-AS1 (HGNC:53716): (IL6R antisense RNA 1)

IL6R-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-154405680-A-G is Benign according to our data. Variant chr1-154405680-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1164781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.722 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6R	NM_000565.4 linkuse as main transcript	c.51A>G	p.Gly17=	synonymous_variant	1/10	ENST00000368485.8
IL6R-AS1	NR_147855.1 linkuse as main transcript	n.126+759T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6R	ENST00000368485.8 linkuse as main transcript	c.51A>G	p.Gly17=	synonymous_variant	1/10	1	NM_000565.4	P1	P08887-1
IL6R-AS1	ENST00000424435.1 linkuse as main transcript	n.126+759T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00346

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00348

AC:

430

AN:

123670

Hom.:

AF XY:

0.00321

AC XY:

219

AN XY:

68204

show subpopulations

Gnomad AFR exome

AF:

0.000403

Gnomad AMR exome

AF:

0.00271

Gnomad ASJ exome

AF:

0.0225

Gnomad EAS exome

AF:

0.000103

Gnomad SAS exome

AF:

0.0000908

Gnomad FIN exome

AF:

0.000563

Gnomad NFE exome

AF:

0.00360

Gnomad OTH exome

AF:

0.00471

GnomAD4 exome

AF:

0.00396

AC:

5449

AN:

1376136

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

2603

AN XY:

679126

show subpopulations

Gnomad4 AFR exome

AF:

0.000493

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.0247

Gnomad4 EAS exome

AF:

0.0000859

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.000447

Gnomad4 NFE exome

AF:

0.00414

Gnomad4 OTH exome

AF:

0.00422

GnomAD4 genome

AF:

0.00274

AC:

417

AN:

152150

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.000747

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00346

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00535

Hom.:

Bravo

AF:

0.00306

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	IL6R: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

IL6R-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 23, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

Cadd

Benign

9.4

Dann

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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