dbSNP rs2069851: IL6:c.*112G>A (chr7-22731685-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000600.5(IL6):c.*112G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000365 in 529,390 control chromosomes in the GnomAD database, including 2 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 0.00087 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

IL6
NM_000600.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.372

Publications

1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BS2

High AC in GnomAd4 at 133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
IL6	NM_000600.5 link	c.*112G>A	3_prime_UTR_variant	Exon 5 of 5	ENST00000258743.10	NP_000591.1
IL6	NM_001371096.1 link	c.*112G>A	3_prime_UTR_variant	Exon 5 of 5		NP_001358025.1
IL6	NM_001318095.2 link	c.*112G>A	3_prime_UTR_variant	Exon 4 of 4		NP_001305024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10 link	c.*112G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_000600.5	ENSP00000258743.5

Frequencies

GnomAD3 genomes

AF:

0.000868

AC:

132

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00304

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000159

AC:

AN:

377122

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

188000

show subpopulations

African (AFR)

AF:

0.00333

AC:

AN:

9300

American (AMR)

AF:

0.000392

AC:

AN:

7650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10002

East Asian (EAS)

AF:

0.0000431

AC:

AN:

23194

South Asian (SAS)

AF:

0.000780

AC:

AN:

5126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29880

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1652

European-Non Finnish (NFE)

AF:

0.0000444

AC:

AN:

269978

Other (OTH)

AF:

0.000442

AC:

AN:

20340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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

AF:

0.000873

AC:

133

AN:

152268

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00306

AC:

127

AN:

41544

American (AMR)

AF:

0.0000654

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000420

Hom.:

Bravo

AF:

0.000850

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.2

(source)

DANN

Benign

0.73

PhyloP100

-0.37

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over