Genetic Variant IL6:p.Asp162Glu (chr7-22731420-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000600.5(IL6):c.486T>G(p.Asp162Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,421,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D162V) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

IL6
NM_000600.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.208

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06264794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6	NM_000600.5 link	c.486T>G	p.Asp162Glu	missense_variant	Exon 5 of 5	ENST00000258743.10	NP_000591.1	P05231Q75MH2B4DVM1
IL6	NM_001371096.1 link	c.417T>G	p.Asp139Glu	missense_variant	Exon 5 of 5		NP_001358025.1
IL6	NM_001318095.2 link	c.258T>G	p.Asp86Glu	missense_variant	Exon 4 of 4		NP_001305024.1	B5MC21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10 link	c.486T>G	p.Asp162Glu	missense_variant	Exon 5 of 5	1	NM_000600.5	ENSP00000258743.5		P05231

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1421872

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704576

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32226

American (AMR)

AF:

0.00

AC:

AN:

39282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24926

East Asian (EAS)

AF:

0.00

AC:

AN:

38942

South Asian (SAS)

AF:

0.00

AC:

AN:

82460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5572

European-Non Finnish (NFE)

AF:

9.20e-7

AC:

AN:

1087406

Other (OTH)

AF:

0.00

AC:

AN:

58326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.1

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.13

T;T;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.50

.;T;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.063

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

N;N;.;.

PhyloP100

-0.21

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.97

N;N;N;N

REVEL

Benign

0.040

Sift

Benign

0.40

T;T;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.0010

B;B;.;.

Vest4

0.0070

MutPred

0.10

Gain of MoRF binding (P = 0.1384);Gain of MoRF binding (P = 0.1384);.;.;

MVP

0.25

MPC

0.16

ClinPred

0.028

GERP RS

-5.8

Varity_R

0.31

gMVP

0.064

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over