rs2228145

Variant summary

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

The NM_000565(IL6R):c.1073A>C(p.Asp358Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151302 control chromosomes in the gnomAD Genomes database, including 9020 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D358Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.32 ( 9020 hom., cov: 30)

Exomes 𝑓: 0.38 ( 19150 hom. )

Consequence

IL6R
NM_000565 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:2

Conservation

PhyloP100: 0.519

Links

IL6R (HGNC:6019):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2167276E-4).

BP6

Variant 1:154454494-A>C is Benign according to our data. Variant chr1-154454494-A-C is described in ClinVar as [Benign]. Clinvar id is 14660. Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6R	NM_000565.4 linkuse as main transcript	c.1073A>C	p.Asp358Ala	missense_variant	9/10	ENST00000368485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6R	ENST00000368485.8 linkuse as main transcript	c.1073A>C	p.Asp358Ala	missense_variant	9/10	1	NM_000565.4	P1	P08887-1

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48587

AN:

151302

Hom.:

9020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.346

GnomAD3 exomes

AF:

0.379

AC:

94659

AN:

249648

Hom.:

19150

AF XY:

0.376

AC XY:

50669

AN XY:

134926

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.550

Gnomad ASJ exome

AF:

0.412

Gnomad EAS exome

AF:

0.381

Gnomad SAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.289

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.390

AC:

565992

AN:

1453118

Hom.:

113611

AF XY:

0.387

AC XY:

279734

AN XY:

723282

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.544

Gnomad4 ASJ exome

AF:

0.415

Gnomad4 EAS exome

AF:

0.392

Gnomad4 SAS exome

AF:

0.307

Gnomad4 FIN exome

AF:

0.293

Gnomad4 NFE exome

AF:

0.403

Gnomad4 OTH exome

AF:

0.369

Alfa

AF:

0.388

Hom.:

19659

Bravo

AF:

0.335

TwinsUK

AF:

0.424

AC:

1571

ALSPAC

AF:

0.425

AC:

1639

ESP6500AA

AF:

0.145

AC:

641

ESP6500EA

AF:

0.405

AC:

3480

ExAC

AF:

0.369

AC:

44828

Asia WGS

AF:

0.286

AC:

998

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 04, 2022

- -

Interleukin 6, serum level of, quantitative trait locus

Other:1

association, no assertion criteria provided

literature only

OMIM

Apr 01, 2007

- -

Soluble interleukin-6 receptor, serum level of, quantitative trait locus

Other:1

association, no assertion criteria provided

literature only

OMIM

Apr 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.34

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.48

MetaRNN

Benign

0.00012

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.9

REVEL

Benign

0.091

Sift

Benign

0.24

Sift4G

Benign

0.34

Polyphen

0.12

Vest4

0.29

MPC

0.33

ClinPred

0.0088

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.20

Splicing

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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over