Genetic Variant NM_000600.5:c.471+715G>A (chr7-22730375-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+715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 813,056 control chromosomes in the GnomAD database, including 725 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 0.055 ( 416 hom., cov: 32)

Exomes 𝑓: 0.025 ( 309 hom. )

Consequence

IL6
NM_000600.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.145

Publications

25 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 = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL6	NM_000600.5 link	c.471+715G>A	intron_variant	Intron 4 of 4	ENST00000258743.10	NP_000591.1	P05231Q75MH2B4DVM1
IL6	XM_005249745.6 link	c.*589G>A	3_prime_UTR_variant	Exon 3 of 3		XP_005249802.1	B4DNQ5
IL6	NM_001371096.1 link	c.402+715G>A	intron_variant	Intron 4 of 4		NP_001358025.1
IL6	NM_001318095.2 link	c.243+715G>A	intron_variant	Intron 3 of 3		NP_001305024.1	B5MC21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10 link	c.471+715G>A		intron_variant	Intron 4 of 4	1	NM_000600.5	ENSP00000258743.5		P05231

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8352

AN:

152082

Hom.:

415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0502

Gnomad ASJ

AF:

0.0703

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0568

Gnomad FIN

AF:

0.0219

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0220

Gnomad OTH

AF:

0.0483

GnomAD4 exome

AF:

0.0245

AC:

16205

AN:

660856

Hom.:

309

Cov.:

AF XY:

0.0243

AC XY:

7493

AN XY:

307854

show subpopulations

African (AFR)

AF:

0.137

AC:

1669

AN:

12212

American (AMR)

AF:

0.0592

AC:

AN:

760

Ashkenazi Jewish (ASJ)

AF:

0.0684

AC:

277

AN:

4050

East Asian (EAS)

AF:

0.000703

AC:

AN:

2844

South Asian (SAS)

AF:

0.0513

AC:

665

AN:

12972

European-Finnish (FIN)

AF:

0.0177

AC:

AN:

226

Middle Eastern (MID)

AF:

0.0282

AC:

AN:

1278

European-Non Finnish (NFE)

AF:

0.0213

AC:

12877

AN:

604794

Other (OTH)

AF:

0.0290

AC:

630

AN:

21720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

729

1458

2186

2915

3644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.0550

AC:

8365

AN:

152200

Hom.:

416

Cov.:

AF XY:

0.0548

AC XY:

4078

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.126

AC:

5231

AN:

41500

American (AMR)

AF:

0.0506

AC:

774

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0703

AC:

244

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5184

South Asian (SAS)

AF:

0.0567

AC:

273

AN:

4818

European-Finnish (FIN)

AF:

0.0219

AC:

232

AN:

10600

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0219

AC:

1492

AN:

68006

Other (OTH)

AF:

0.0473

AC:

100

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

380

760

1139

1519

1899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0302

Hom.:

158

Bravo

AF:

0.0619

Asia WGS

AF:

0.0320

AC:

113

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.9

(source)

DANN

Benign

0.41

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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