rs12730935

Variant summary

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

The NM_000565.4(IL6R):​c.950-709G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.28 ( 5191 hom., cov: 15)

Consequence

IL6R
NM_000565.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.281
Variant links:
Genes affected
IL6R (HGNC:6019): (interleukin 6 receptor) This gene encodes a subunit of the interleukin 6 (IL6) receptor complex. Interleukin 6 is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in the immune response. The IL6 receptor is a protein complex consisting of this protein and interleukin 6 signal transducer (IL6ST/GP130/IL6-beta), a receptor subunit also shared by many other cytokines. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer. Alternatively spliced transcript variants encoding distinct isoforms have been identified in this gene. A pseudogene of this gene is found on chromosome 9. [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=-1.0).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL6RNM_000565.4 linkc.950-709G>A intron_variant Intron 6 of 9 ENST00000368485.8 NP_000556.1 P08887-1A0N0L5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL6RENST00000368485.8 linkc.950-709G>A intron_variant Intron 6 of 9 1 NM_000565.4 ENSP00000357470.3 P08887-1

Frequencies

GnomAD3 genomes
AF:
0.278
AC:
28707
AN:
103118
Hom.:
5192
Cov.:
15
show subpopulations
Gnomad AFR
AF:
0.0976
Gnomad AMI
AF:
0.411
Gnomad AMR
AF:
0.444
Gnomad ASJ
AF:
0.359
Gnomad EAS
AF:
0.291
Gnomad SAS
AF:
0.225
Gnomad FIN
AF:
0.213
Gnomad MID
AF:
0.418
Gnomad NFE
AF:
0.349
Gnomad OTH
AF:
0.306
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.278
AC:
28697
AN:
103160
Hom.:
5191
Cov.:
15
AF XY:
0.271
AC XY:
12963
AN XY:
47922
show subpopulations
Gnomad4 AFR
AF:
0.0973
Gnomad4 AMR
AF:
0.444
Gnomad4 ASJ
AF:
0.359
Gnomad4 EAS
AF:
0.290
Gnomad4 SAS
AF:
0.224
Gnomad4 FIN
AF:
0.213
Gnomad4 NFE
AF:
0.349
Gnomad4 OTH
AF:
0.303
Alfa
AF:
0.0501
Hom.:
58

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.84
DANN
Benign
0.48

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: rs12730935; hg19: chr1-154419892; COSMIC: COSV59818981; API