rs2069860

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000600.5(IL6):c.485A>T(p.Asp162Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,573,798 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D162E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0055 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0076 ( 53 hom. )

Consequence

IL6
NM_000600.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.193

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041643977).

BP6

Variant 7-22731419-A-T is Benign according to our data. Variant chr7-22731419-A-T is described in ClinVar as [Benign]. Clinvar id is 777811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 835 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6	NM_000600.5 link	c.485A>T	p.Asp162Val	missense_variant	Exon 5 of 5	ENST00000258743.10	NP_000591.1	P05231Q75MH2B4DVM1
IL6	NM_001371096.1 link	c.416A>T	p.Asp139Val	missense_variant	Exon 5 of 5		NP_001358025.1
IL6	NM_001318095.2 link	c.257A>T	p.Asp86Val	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.485A>T	p.Asp162Val	missense_variant	Exon 5 of 5	1	NM_000600.5	ENSP00000258743.5		P05231

Frequencies

GnomAD3 genomes

AF:

0.00548

AC:

834

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.00641

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00844

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00597

AC:

1404

AN:

235312

Hom.:

AF XY:

0.00656

AC XY:

839

AN XY:

127898

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.000557

Gnomad EAS exome

AF:

0.000174

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.00743

Gnomad NFE exome

AF:

0.00757

Gnomad OTH exome

AF:

0.00631

GnomAD4 exome

AF:

0.00762

AC:

10831

AN:

1421522

Hom.:

Cov.:

AF XY:

0.00769

AC XY:

5416

AN XY:

704344

show subpopulations

Gnomad4 AFR exome

AF:

0.000869

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.000281

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.00796

Gnomad4 NFE exome

AF:

0.00832

Gnomad4 OTH exome

AF:

0.00722

GnomAD4 genome

AF:

0.00548

AC:

835

AN:

152276

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

429

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.00641

Gnomad4 NFE

AF:

0.00844

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00713

Hom.:

Bravo

AF:

0.00483

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00814

AC:

ExAC

AF:

0.00612

AC:

743

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2025	IL6: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.9

DANN

Benign

0.50

DEOGEN2

Benign

0.22

T;T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.68

.;T;T;T

MetaRNN

Benign

0.0042

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

N;N;.;.

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-3.6

D;D;D;D

REVEL

Benign

0.020

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.083

T;T;T;T

Polyphen

0.0080

B;B;.;.

Vest4

0.17

MVP

0.25

MPC

0.25

ClinPred

0.0059

GERP RS

0.44

Varity_R

0.53

gMVP

0.34

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