dbSNP rs2069840: IL6:c.324+147C>G (chr7-22728953-C-G) – 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.324+147C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 631,248 control chromosomes in the GnomAD database, including 28,463 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 0.27 ( 6315 hom., cov: 33)

Exomes 𝑓: 0.29 ( 22148 hom. )

Consequence

IL6
NM_000600.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.509

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:

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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=-0.64).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL6	NM_000600.5 link	c.324+147C>G	intron_variant	Intron 3 of 4	ENST00000258743.10	NP_000591.1	P05231Q75MH2B4DVM1
IL6	NM_001371096.1 link	c.255+147C>G	intron_variant	Intron 3 of 4		NP_001358025.1
IL6	NM_001318095.2 link	c.96+147C>G	intron_variant	Intron 2 of 3		NP_001305024.1	B5MC21
IL6	XM_005249745.6 link	c.486+147C>G	intron_variant	Intron 2 of 2		XP_005249802.1	B4DNQ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10 link	c.324+147C>G		intron_variant	Intron 3 of 4	1	NM_000600.5	ENSP00000258743.5		P05231

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41529

AN:

152042

Hom.:

6317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.0647

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.352

Gnomad OTH

AF:

0.281

GnomAD4 exome

AF:

0.290

AC:

138704

AN:

479088

Hom.:

22148

AF XY:

0.286

AC XY:

72511

AN XY:

253444

show subpopulations

Gnomad4 AFR exome

AF:

0.167

AC:

2196

AN:

13152

Gnomad4 AMR exome

AF:

0.340

AC:

7792

AN:

22940

Gnomad4 ASJ exome

AF:

0.250

AC:

3689

AN:

14772

Gnomad4 EAS exome

AF:

0.0675

AC:

2116

AN:

31364

Gnomad4 SAS exome

AF:

0.191

AC:

9230

AN:

48208

Gnomad4 FIN exome

AF:

0.241

AC:

9435

AN:

39188

Gnomad4 NFE exome

AF:

0.343

AC:

95561

AN:

278730

Gnomad4 Remaining exome

AF:

0.291

AC:

7892

AN:

27078

Heterozygous variant carriers

4575

9151

13726

18302

22877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.273

AC:

41526

AN:

152160

Hom.:

6315

Cov.:

AF XY:

0.268

AC XY:

19915

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.166

AC:

0.165695

AN:

0.165695

Gnomad4 AMR

AF:

0.344

AC:

0.34402

AN:

0.34402

Gnomad4 ASJ

AF:

0.262

AC:

0.261521

AN:

0.261521

Gnomad4 EAS

AF:

0.0648

AC:

0.0648148

AN:

0.0648148

Gnomad4 SAS

AF:

0.174

AC:

0.173651

AN:

0.173651

Gnomad4 FIN

AF:

0.234

AC:

0.233711

AN:

0.233711

Gnomad4 NFE

AF:

0.352

AC:

0.35204

AN:

0.35204

Gnomad4 OTH

AF:

0.277

AC:

0.2772

AN:

0.2772

Heterozygous variant carriers

1522

3044

4565

6087

7609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.307

Hom.:

1038

Bravo

AF:

0.277

Asia WGS

AF:

0.124

AC:

431

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.81

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over