chr1-154447416-G-A

Variant summary

Our verdict is Benign. The variant received -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

Publications

25 publications found
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]
IL6R Gene-Disease associations (from GenCC):
  • hyper-IgE recurrent infection syndrome 5, autosomal recessive
    Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

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=-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
African (AFR)
AF:
0.0973
AC:
2683
AN:
27562
American (AMR)
AF:
0.444
AC:
3687
AN:
8296
Ashkenazi Jewish (ASJ)
AF:
0.359
AC:
942
AN:
2626
East Asian (EAS)
AF:
0.290
AC:
966
AN:
3326
South Asian (SAS)
AF:
0.224
AC:
689
AN:
3082
European-Finnish (FIN)
AF:
0.213
AC:
939
AN:
4400
Middle Eastern (MID)
AF:
0.422
AC:
70
AN:
166
European-Non Finnish (NFE)
AF:
0.349
AC:
18029
AN:
51652
Other (OTH)
AF:
0.303
AC:
420
AN:
1388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.448
Heterozygous variant carriers
0
631
1262
1892
2523
3154
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
258
516
774
1032
1290
<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:
0.0159
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
PhyloP100
-0.28
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

Other links and lift over

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