dbSNP rs2069842: IL6:c.471+31G>A (chr7-22729691-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

24 publications found

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 Gene-Disease associations (from GenCC):

Kaposi sarcoma, susceptibility to
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P

IL6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein
IL6	NM_000600.5 link	c.471+31G>A		intron_variant	Intron 4 of 4	ENST00000258743.10	NP_000591.1
IL6	XM_005249745.6 link	c.664G>A	p.Val222Met	missense_variant	Exon 3 of 3		XP_005249802.1
IL6	NM_001371096.1 link	c.402+31G>A		intron_variant	Intron 4 of 4		NP_001358025.1
IL6	NM_001318095.2 link	c.243+31G>A		intron_variant	Intron 3 of 3		NP_001305024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10 link	c.471+31G>A		intron_variant	Intron 4 of 4	1	NM_000600.5	ENSP00000258743.5

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

GnomAD2 exomes

AF:

0.00618

AC:

1552

AN:

251248

AF XY:

0.00434

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 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

African (AFR)

AF:

0.0791

AC:

2646

AN:

33472

American (AMR)

AF:

0.00492

AC:

220

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00233

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000185

AC:

206

AN:

1111918

Other (OTH)

AF:

0.00568

AC:

343

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

186

371

557

742

928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0219

AC:

3334

AN:

152310

Hom.:

124

Cov.:

AF XY:

0.0213

AC XY:

1583

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0757

AC:

3147

AN:

41550

American (AMR)

AF:

0.00817

AC:

125

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000323

AC:

AN:

68024

Other (OTH)

AF:

0.0161

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

157

315

472

630

787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0171

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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.52

(source)

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

PhyloP100

-1.3

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over