1-154405680-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000565.4(IL6R):c.51A>G(p.Gly17Gly) 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:4

Conservation

PhyloP100: -0.722

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -17 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.

BS2

High Homozygotes in GnomAdExome4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4 link	c.51A>G	p.Gly17Gly	synonymous_variant	Exon 1 of 10	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.51A>G	p.Gly17Gly	synonymous_variant	Exon 1 of 10	1	NM_000565.4	ENSP00000357470.3		P08887-1

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

GnomAD2 exomes

AF:

0.00348

AC:

430

AN:

123670

AF XY:

0.00321

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 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

African (AFR)

AF:

0.000493

AC:

AN:

30410

American (AMR)

AF:

0.00266

AC:

AN:

35354

Ashkenazi Jewish (ASJ)

AF:

0.0247

AC:

611

AN:

24712

East Asian (EAS)

AF:

0.0000859

AC:

AN:

34944

South Asian (SAS)

AF:

0.000152

AC:

AN:

78828

European-Finnish (FIN)

AF:

0.000447

AC:

AN:

33536

Middle Eastern (MID)

AF:

0.000463

AC:

AN:

4322

European-Non Finnish (NFE)

AF:

0.00414

AC:

4455

AN:

1076618

Other (OTH)

AF:

0.00422

AC:

242

AN:

57412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

275

549

824

1098

1373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00274

AC:

417

AN:

152150

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.000747

AC:

AN:

41514

American (AMR)

AF:

0.00379

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

AN:

3466

East Asian (EAS)

AF:

0.000194

AC:

AN:

5152

South Asian (SAS)

AF:

0.000415

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00346

AC:

235

AN:

67980

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IL6R: BP4, BP7, BS2 -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

IL6R-related disorder

Benign:1

Jan 23, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.69

PhyloP100

-0.72

PromoterAI

-0.13

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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1-154405680-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over