Variant rs2069842 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000600.5(IL6):c.471+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 1,614,056 control chromosomes in the GnomAD database, including 240 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.022 ( 124 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 116 hom. )

Consequence

IL6
NM_000600.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.32

Variant links:

Genes affected

IL6 (HGNC:6018): (interleukin 6) This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Elevated levels of the encoded protein have been found in virus infections, including COVID-19 (disease caused by SARS-CoV-2). [provided by RefSeq, Aug 2020]

IL6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017405152).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IL6	NM_000600.5 linkuse as main transcript	c.471+31G>A		intron_variant		ENST00000258743.10	NP_000591.1
IL6	XM_005249745.6 linkuse as main transcript	c.664G>A	p.Val222Met	missense_variant	3/3		XP_005249802.1
IL6	NM_001318095.2 linkuse as main transcript	c.243+31G>A		intron_variant			NP_001305024.1
IL6	NM_001371096.1 linkuse as main transcript	c.402+31G>A		intron_variant			NP_001358025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10 linkuse as main transcript	c.471+31G>A		intron_variant		1	NM_000600.5	ENSP00000258743	P1

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3336

AN:

152192

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0760

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0162

GnomAD3 exomes

AF:

0.00618

AC:

1552

AN:

251248

Hom.:

AF XY:

0.00434

AC XY:

589

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0800

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00240

AC:

3504

AN:

1461746

Hom.:

116

Cov.:

AF XY:

0.00208

AC XY:

1511

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0791

Gnomad4 AMR exome

AF:

0.00492

Gnomad4 ASJ exome

AF:

0.00233

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000185

Gnomad4 OTH exome

AF:

0.00568

GnomAD4 genome

AF:

0.0219

AC:

3334

AN:

152310

Hom.:

124

Cov.:

AF XY:

0.0213

AC XY:

1583

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0757

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.0251

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0713

AC:

314

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00737

AC:

895

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.52

DANN

Benign

0.54

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.53

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PROVEAN

Benign

-0.13

N;N

REVEL

Benign

0.027

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

0.0060

.;B

Vest4

0.13

MVP

0.36

ClinPred

0.0078

GERP RS

-5.3

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over