chr1-154428323-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000565.4(IL6R):​c.86-873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,858 control chromosomes in the GnomAD database, including 25,096 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 0.57 ( 25096 hom., cov: 31)

Consequence

IL6R
NM_000565.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58

Publications

26 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=-0.92).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL6RNM_000565.4 linkc.86-873T>C intron_variant Intron 1 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.86-873T>C intron_variant Intron 1 of 9 1 NM_000565.4 ENSP00000357470.3 P08887-1
IL6RENST00000344086.8 linkc.86-873T>C intron_variant Intron 1 of 8 1 ENSP00000340589.4 P08887-2
IL6RENST00000622330.5 linkc.86-873T>C intron_variant Intron 1 of 6 1 ENSP00000477739.1 A0A087WTB5
IL6RENST00000512471.1 linkc.86-873T>C intron_variant Intron 1 of 3 4 ENSP00000423184.1 D6R9R8

Frequencies

GnomAD3 genomes
AF:
0.572
AC:
86733
AN:
151740
Hom.:
25060
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.599
Gnomad AMI
AF:
0.688
Gnomad AMR
AF:
0.644
Gnomad ASJ
AF:
0.584
Gnomad EAS
AF:
0.486
Gnomad SAS
AF:
0.461
Gnomad FIN
AF:
0.453
Gnomad MID
AF:
0.551
Gnomad NFE
AF:
0.569
Gnomad OTH
AF:
0.558
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.572
AC:
86825
AN:
151858
Hom.:
25096
Cov.:
31
AF XY:
0.563
AC XY:
41789
AN XY:
74196
show subpopulations
African (AFR)
AF:
0.600
AC:
24832
AN:
41404
American (AMR)
AF:
0.644
AC:
9832
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
0.584
AC:
2023
AN:
3466
East Asian (EAS)
AF:
0.487
AC:
2505
AN:
5144
South Asian (SAS)
AF:
0.462
AC:
2223
AN:
4808
European-Finnish (FIN)
AF:
0.453
AC:
4783
AN:
10550
Middle Eastern (MID)
AF:
0.551
AC:
162
AN:
294
European-Non Finnish (NFE)
AF:
0.569
AC:
38665
AN:
67906
Other (OTH)
AF:
0.557
AC:
1174
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1865
3731
5596
7462
9327
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
732
1464
2196
2928
3660
<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:
0.572
Hom.:
12975
Bravo
AF:
0.593
Asia WGS
AF:
0.483
AC:
1682
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.054
DANN
Benign
0.49
PhyloP100
-1.6
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: rs6427658; hg19: chr1-154400799; API