dbSNP rs7802308: IL6-AS1:n.54-110A>T (chr7-22726815-T-A) – 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.54-110A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 146,400 control chromosomes in the GnomAD database, including 5,183 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 0.24 ( 4991 hom., cov: 31)

Exomes 𝑓: 0.16 ( 192 hom. )

Consequence

IL6-AS1
ENST00000325042.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.979

Publications

10 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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6-AS1	NR_131935.1 link	n.54-110A>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
IL6-AS1	ENST00000325042.2 link	n.54-110A>T	intron_variant	Intron 1 of 1	1
IL6	ENST00000404625.5 link	c.-84-364T>A	intron_variant	Intron 1 of 5	5	ENSP00000385675.1	P05231
STEAP1B	ENST00000650428.1 link	n.46+753A>T	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

33716

AN:

138878

Hom.:

4991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.789

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.406

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.275

GnomAD4 exome

AF:

0.160

AC:

1184

AN:

7420

Hom.:

192

AF XY:

0.160

AC XY:

612

AN XY:

3818

show subpopulations

African (AFR)

AF:

0.303

AC:

AN:

178

American (AMR)

AF:

0.259

AC:

154

AN:

594

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

AN:

218

East Asian (EAS)

AF:

0.759

AC:

173

AN:

228

South Asian (SAS)

AF:

0.402

AC:

AN:

224

European-Finnish (FIN)

AF:

0.107

AC:

AN:

318

Middle Eastern (MID)

AF:

0.214

AC:

AN:

European-Non Finnish (NFE)

AF:

0.107

AC:

560

AN:

5220

Other (OTH)

AF:

0.175

AC:

AN:

412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

133

178

222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.243

AC:

33748

AN:

138980

Hom.:

4991

Cov.:

AF XY:

0.252

AC XY:

17134

AN XY:

67972

show subpopulations

African (AFR)

AF:

0.296

AC:

10638

AN:

35980

American (AMR)

AF:

0.311

AC:

4440

AN:

14278

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

942

AN:

3326

East Asian (EAS)

AF:

0.789

AC:

3981

AN:

5048

South Asian (SAS)

AF:

0.468

AC:

2110

AN:

4510

European-Finnish (FIN)

AF:

0.163

AC:

1618

AN:

9902

Middle Eastern (MID)

AF:

0.403

AC:

108

AN:

268

European-Non Finnish (NFE)

AF:

0.146

AC:

9161

AN:

62878

Other (OTH)

AF:

0.275

AC:

537

AN:

1950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1166

2332

3497

4663

5829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.185

Hom.:

340

Asia WGS

AF:

0.543

AC:

1888

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.8

(source)

DANN

Benign

0.17

PhyloP100

0.98

PromoterAI

0.020

Neutral

(source)

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