Variant chr1-154429203-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000565.4(IL6R):c.93G>A(p.Ala31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,610,256 control chromosomes in the GnomAD database, including 18,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1439 hom., cov: 31)

Exomes 𝑓: 0.15 ( 17504 hom. )

Consequence

IL6R
NM_000565.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.21

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-154429203-G-A is Benign according to our data. Variant chr1-154429203-G-A is described in ClinVar as [Benign]. Clinvar id is 1164401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 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.93G>A	p.Ala31=	synonymous_variant	2/10	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.93G>A	p.Ala31=	synonymous_variant	2/10	1	NM_000565.4	ENSP00000357470	P1	P08887-1
IL6R	ENST00000344086.8 linkuse as main transcript	c.93G>A	p.Ala31=	synonymous_variant	2/9	1		ENSP00000340589		P08887-2
IL6R	ENST00000622330.5 linkuse as main transcript	c.93G>A	p.Ala31=	synonymous_variant	2/7	1		ENSP00000477739
IL6R	ENST00000512471.1 linkuse as main transcript	c.93G>A	p.Ala31=	synonymous_variant	2/4	4		ENSP00000423184

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19471

AN:

151990

Hom.:

1436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0623

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.139

AC:

34830

AN:

250842

Hom.:

2700

AF XY:

0.141

AC XY:

19133

AN XY:

135578

show subpopulations

Gnomad AFR exome

AF:

0.0603

Gnomad AMR exome

AF:

0.0767

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.113

Gnomad SAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.163

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.152

AC:

222252

AN:

1458148

Hom.:

17504

Cov.:

AF XY:

0.152

AC XY:

110365

AN XY:

724486

show subpopulations

Gnomad4 AFR exome

AF:

0.0549

Gnomad4 AMR exome

AF:

0.0799

Gnomad4 ASJ exome

AF:

0.175

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.159

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.128

AC:

19480

AN:

152108

Hom.:

1439

Cov.:

AF XY:

0.128

AC XY:

9508

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0621

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.163

Gnomad4 OTH

AF:

0.132

Alfa

AF:

0.152

Hom.:

1919

Bravo

AF:

0.120

Asia WGS

AF:

0.157

AC:

545

AN:

3478

EpiCase

AF:

0.164

EpiControl

AF:

0.160

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

IL6R-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as 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

-0.84

CADD

Benign

1.6

DANN

Benign

0.41

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