Genetic Variant IL6-AS1:n.132C>G (chr7-22726627-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000325042.2(IL6-AS1):n.132C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 155,688 control chromosomes in the GnomAD database, including 2,496 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 0.11 ( 2425 hom., cov: 32)

Exomes 𝑓: 0.10 ( 71 hom. )

Consequence

IL6-AS1
ENST00000325042.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.753

Publications

1044 publications found

Variant links:

Genes affected

IL6-AS1 (HGNC:40301): (IL6 antisense RNA 1)

IL6-AS1 links:

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:

STEAP1B (HGNC:41907): (STEAP family member 1B) Predicted to be integral component of membrane. Predicted to be active in endosome and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

STEAP1B 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6-AS1	NR_131935.1 link	n.132C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
IL6-AS1	ENST00000325042.2 link	n.132C>G	non_coding_transcript_exon_variant	Exon 2 of 2	1
IL6	ENST00000404625.5 link	c.-85+369G>C	intron_variant	Intron 1 of 5	5	ENSP00000385675.1
STEAP1B	ENST00000650428.1 link	n.46+941C>G	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16788

AN:

152092

Hom.:

2431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0933

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.0812

Gnomad EAS

AF:

0.761

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.0258

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0497

Gnomad OTH

AF:

0.123

GnomAD4 exome

AF:

0.100

AC:

349

AN:

3478

Hom.:

Cov.:

AF XY:

0.0911

AC XY:

168

AN XY:

1844

show subpopulations

African (AFR)

AF:

0.0682

AC:

AN:

American (AMR)

AF:

0.175

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0686

AC:

AN:

102

East Asian (EAS)

AF:

0.719

AC:

174

AN:

242

South Asian (SAS)

AF:

0.375

AC:

AN:

European-Finnish (FIN)

AF:

0.0237

AC:

AN:

380

Middle Eastern (MID)

AF:

0.150

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0472

AC:

111

AN:

2354

Other (OTH)

AF:

0.0851

AC:

AN:

188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.110

AC:

16809

AN:

152210

Hom.:

2425

Cov.:

AF XY:

0.118

AC XY:

8758

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0934

AC:

3877

AN:

41522

American (AMR)

AF:

0.202

AC:

3087

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0812

AC:

282

AN:

3472

East Asian (EAS)

AF:

0.761

AC:

3933

AN:

5170

South Asian (SAS)

AF:

0.335

AC:

1615

AN:

4818

European-Finnish (FIN)

AF:

0.0258

AC:

274

AN:

10602

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0497

AC:

3383

AN:

68012

Other (OTH)

AF:

0.125

AC:

265

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

613

1226

1838

2451

3064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<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:

0.0709

Hom.:

107

Bravo

AF:

0.122

Asia WGS

AF:

0.492

AC:

1708

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.6

(source)

DANN

Benign

0.46

PhyloP100

0.75

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over