rs2069835

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000600.5(IL6):​c.211-441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 152,194 control chromosomes in the GnomAD database, including 478 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 0.075 ( 478 hom., cov: 32)

Consequence

IL6
NM_000600.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.999
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL6NM_000600.5 linkuse as main transcriptc.211-441T>C intron_variant ENST00000258743.10
IL6NM_001318095.2 linkuse as main transcriptc.-18-441T>C intron_variant
IL6NM_001371096.1 linkuse as main transcriptc.142-441T>C intron_variant
IL6XM_005249745.6 linkuse as main transcriptc.373-441T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL6ENST00000258743.10 linkuse as main transcriptc.211-441T>C intron_variant 1 NM_000600.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0753
AC:
11447
AN:
152076
Hom.:
477
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.101
Gnomad AMI
AF:
0.146
Gnomad AMR
AF:
0.0540
Gnomad ASJ
AF:
0.123
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.0671
Gnomad FIN
AF:
0.125
Gnomad MID
AF:
0.191
Gnomad NFE
AF:
0.0590
Gnomad OTH
AF:
0.0750
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0752
AC:
11447
AN:
152194
Hom.:
478
Cov.:
32
AF XY:
0.0763
AC XY:
5681
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.101
Gnomad4 AMR
AF:
0.0540
Gnomad4 ASJ
AF:
0.123
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.0674
Gnomad4 FIN
AF:
0.125
Gnomad4 NFE
AF:
0.0590
Gnomad4 OTH
AF:
0.0737
Alfa
AF:
0.0663
Hom.:
252
Bravo
AF:
0.0733
Asia WGS
AF:
0.0270
AC:
95
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
9.1
DANN
Benign
0.49

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.

Other links and lift over

dbSNP: rs2069835; hg19: chr7-22767871; API