7-22731419-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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

Publications

33 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 -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 VariationId is 777811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 835 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000600.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL6	NM_000600.5	MANE Select	c.485A>T	p.Asp162Val	missense	Exon 5 of 5	NP_000591.1	P05231
IL6	NM_001371096.1		c.416A>T	p.Asp139Val	missense	Exon 5 of 5	NP_001358025.1	B5MCZ3
IL6	NM_001318095.2		c.257A>T	p.Asp86Val	missense	Exon 4 of 4	NP_001305024.1	B5MC21

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL6	ENST00000258743.10	TSL:1 MANE Select	c.485A>T	p.Asp162Val	missense	Exon 5 of 5	ENSP00000258743.5	P05231
IL6	ENST00000485300.1	TSL:1	c.647A>T	p.Asp216Val	missense	Exon 4 of 4	ENSP00000512964.1	A0A8Q3SJL1
IL6	ENST00000404625.5	TSL:5	c.485A>T	p.Asp162Val	missense	Exon 6 of 6	ENSP00000385675.1	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

GnomAD2 exomes

AF:

0.00597

AC:

1404

AN:

235312

AF XY:

0.00656

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 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

African (AFR)

AF:

0.000869

AC:

AN:

32210

American (AMR)

AF:

0.00127

AC:

AN:

39428

Ashkenazi Jewish (ASJ)

AF:

0.000281

AC:

AN:

24896

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38968

South Asian (SAS)

AF:

0.0102

AC:

843

AN:

82406

European-Finnish (FIN)

AF:

0.00796

AC:

420

AN:

52734

Middle Eastern (MID)

AF:

0.00215

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.00832

AC:

9049

AN:

1086974

Other (OTH)

AF:

0.00722

AC:

421

AN:

58332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

459

917

1376

1834

2293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.00548

AC:

835

AN:

152276

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

429

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

41554

American (AMR)

AF:

0.00144

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0122

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00641

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00844

AC:

574

AN:

68020

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

133

177

221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00713

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.9

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.22

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

PhyloP100

-0.19

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.020

Sift

Benign

0.12

Sift4G

Benign

0.083

Polyphen

0.0080

Vest4

0.17

MVP

0.25

MPC

0.25

ClinPred

0.0059

GERP RS

0.44

Varity_R

0.53

gMVP

0.34

Mutation Taster

=94/6

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over