dbSNP rs2069844: IL6:c.471+731C>A (chr7-22730391-C-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+731C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 536,224 control chromosomes in the GnomAD database, including 1,810 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 0.089 ( 1373 hom., cov: 32)

Exomes 𝑓: 0.031 ( 437 hom. )

Consequence

IL6
NM_000600.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.911

Publications

8 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 (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
IL6	NM_000600.5	MANE Select	c.471+731C>A	intron	N/A	NP_000591.1	P05231
IL6	NM_001371096.1		c.402+731C>A	intron	N/A	NP_001358025.1	B5MCZ3
IL6	NM_001318095.2		c.243+731C>A	intron	N/A	NP_001305024.1	B5MC21

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL6	ENST00000258743.10	TSL:1 MANE Select	c.471+731C>A	intron	N/A	ENSP00000258743.5	P05231
IL6	ENST00000485300.1	TSL:1	c.633+731C>A	intron	N/A	ENSP00000512964.1	A0A8Q3SJL1
IL6	ENST00000404625.5	TSL:5	c.471+731C>A	intron	N/A	ENSP00000385675.1	P05231

Frequencies

GnomAD3 genomes

AF:

0.0887

AC:

13482

AN:

152054

Hom.:

1367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0626

Gnomad ASJ

AF:

0.0699

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0580

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0225

Gnomad OTH

AF:

0.0699

GnomAD4 exome

AF:

0.0305

AC:

11724

AN:

384052

Hom.:

437

Cov.:

AF XY:

0.0301

AC XY:

5447

AN XY:

180694

show subpopulations

African (AFR)

AF:

0.281

AC:

2032

AN:

7232

American (AMR)

AF:

0.0700

AC:

AN:

414

Ashkenazi Jewish (ASJ)

AF:

0.0762

AC:

181

AN:

2374

East Asian (EAS)

AF:

0.000618

AC:

AN:

1618

South Asian (SAS)

AF:

0.0595

AC:

454

AN:

7624

European-Finnish (FIN)

AF:

0.0290

AC:

AN:

138

Middle Eastern (MID)

AF:

0.0474

AC:

AN:

760

European-Non Finnish (NFE)

AF:

0.0241

AC:

8463

AN:

351234

Other (OTH)

AF:

0.0414

AC:

524

AN:

12658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

517

1034

1550

2067

2584

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.0888

AC:

13520

AN:

152172

Hom.:

1373

Cov.:

AF XY:

0.0875

AC XY:

6511

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.244

AC:

10111

AN:

41464

American (AMR)

AF:

0.0630

AC:

964

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0699

AC:

242

AN:

3464

East Asian (EAS)

AF:

0.00135

AC:

AN:

5186

South Asian (SAS)

AF:

0.0574

AC:

277

AN:

4824

European-Finnish (FIN)

AF:

0.0218

AC:

231

AN:

10616

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0225

AC:

1528

AN:

68004

Other (OTH)

AF:

0.0687

AC:

145

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

532

1065

1597

2130

2662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0747

Hom.:

829

Bravo

AF:

0.100

Asia WGS

AF:

0.0410

AC:

144

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.63

(source)

DANN

Benign

0.46

PhyloP100

-0.91

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over