chr1-154429236-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_000565.4(IL6R):c.126C>T(p.Ser42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,613,898 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0092 ( 21 hom., cov: 32)
Exomes 𝑓: 0.00091 ( 12 hom. )
Consequence
IL6R
NM_000565.4 synonymous
NM_000565.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.62
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 1-154429236-C-T is Benign according to our data. Variant chr1-154429236-C-T is described in ClinVar as [Benign]. Clinvar id is 715552.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-4.61 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00924 (1406/152230) while in subpopulation AFR AF= 0.0321 (1332/41536). AF 95% confidence interval is 0.0306. There are 21 homozygotes in gnomad4. There are 676 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 21 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL6R | NM_000565.4 | c.126C>T | p.Ser42= | synonymous_variant | 2/10 | ENST00000368485.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL6R | ENST00000368485.8 | c.126C>T | p.Ser42= | synonymous_variant | 2/10 | 1 | NM_000565.4 | P1 | |
IL6R | ENST00000344086.8 | c.126C>T | p.Ser42= | synonymous_variant | 2/9 | 1 | |||
IL6R | ENST00000622330.5 | c.126C>T | p.Ser42= | synonymous_variant | 2/7 | 1 | |||
IL6R | ENST00000512471.1 | c.126C>T | p.Ser42= | synonymous_variant | 2/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00921 AC: 1401AN: 152112Hom.: 21 Cov.: 32
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GnomAD3 exomes AF: 0.00251 AC: 631AN: 251384Hom.: 9 AF XY: 0.00176 AC XY: 239AN XY: 135860
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GnomAD4 exome AF: 0.000912 AC: 1333AN: 1461668Hom.: 12 Cov.: 33 AF XY: 0.000772 AC XY: 561AN XY: 727092
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at