Genetic Variant NM_000600.5:c.-48C>A (chr7-22727215-C-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.-48C>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00171 in 1,611,092 control chromosomes in the GnomAD database, including 4 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 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

IL6
NM_000600.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.91

Publications

11 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 links:

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

IL6-AS1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BS2

High AC in GnomAd4 at 234 AD gene.

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.-48C>A	5_prime_UTR	Exon 1 of 5	NP_000591.1	P05231
IL6	NM_001371096.1		c.-48C>A	5_prime_UTR	Exon 1 of 5	NP_001358025.1	B5MCZ3
IL6	NM_001318095.2		c.-85C>A	5_prime_UTR	Exon 1 of 4	NP_001305024.1	B5MC21

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL6	ENST00000258743.10	TSL:1 MANE Select	c.-48C>A	5_prime_UTR	Exon 1 of 5	ENSP00000258743.5	P05231
IL6	ENST00000485300.1	TSL:1	c.-48C>A	5_prime_UTR	Exon 1 of 4	ENSP00000512964.1	A0A8Q3SJL1
IL6-AS1	ENST00000325042.2	TSL:1	n.53+353G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

234

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00782

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00182

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00185

AC:

464

AN:

250248

AF XY:

0.00192

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00833

Gnomad NFE exome

AF:

0.00214

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00173

AC:

2522

AN:

1458838

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1235

AN XY:

725860

show subpopulations

African (AFR)

AF:

0.000449

AC:

AN:

33382

American (AMR)

AF:

0.000583

AC:

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26024

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000279

AC:

AN:

86126

European-Finnish (FIN)

AF:

0.00746

AC:

398

AN:

53350

Middle Eastern (MID)

AF:

0.00129

AC:

AN:

4654

European-Non Finnish (NFE)

AF:

0.00177

AC:

1967

AN:

1110820

Other (OTH)

AF:

0.00138

AC:

AN:

60190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

123

246

370

493

616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.00154

AC:

234

AN:

152254

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41552

American (AMR)

AF:

0.000327

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00782

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00182

AC:

124

AN:

68010

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.00181

Hom.:

Bravo

AF:

0.000929

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

3.9

PromoterAI

-0.0060

Neutral

(source)

Mutation Taster

=299/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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