6-31576412-A-G
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000594.4(TNF):c.187-122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 916,376 control chromosomes in the GnomAD database, including 2,659 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 0.072 ( 444 hom., cov: 31)
Exomes 𝑓: 0.068 ( 2215 hom. )
Consequence
TNF
NM_000594.4 intron
NM_000594.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.31
Genes affected
TNF (HGNC:11892): (tumor necrosis factor) This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, psoriasis, rheumatoid arthritis ankylosing spondylitis, tuberculosis, autosomal dominant polycystic kidney disease, and cancer. Mutations in this gene affect susceptibility to cerebral malaria, septic shock, and Alzheimer disease. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Aug 2020]
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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=-0.85).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNF | ENST00000449264.3 | c.187-122A>G | intron_variant | Intron 1 of 3 | 1 | NM_000594.4 | ENSP00000398698.2 | |||
TNF | ENST00000699334.1 | c.187-355A>G | intron_variant | Intron 1 of 2 | ENSP00000514308.1 |
Frequencies
GnomAD3 genomes AF: 0.0718 AC: 10920AN: 152064Hom.: 440 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
10920
AN:
152064
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0684 AC: 52241AN: 764194Hom.: 2215 AF XY: 0.0689 AC XY: 27517AN XY: 399246 show subpopulations
GnomAD4 exome
AF:
AC:
52241
AN:
764194
Hom.:
AF XY:
AC XY:
27517
AN XY:
399246
Gnomad4 AFR exome
AF:
AC:
1443
AN:
18864
Gnomad4 AMR exome
AF:
AC:
2133
AN:
29830
Gnomad4 ASJ exome
AF:
AC:
2370
AN:
16716
Gnomad4 EAS exome
AF:
AC:
789
AN:
36510
Gnomad4 SAS exome
AF:
AC:
4343
AN:
59614
Gnomad4 FIN exome
AF:
AC:
904
AN:
43346
Gnomad4 NFE exome
AF:
AC:
36969
AN:
519154
Gnomad4 Remaining exome
AF:
AC:
2915
AN:
36850
Heterozygous variant carriers
0
2475
4950
7426
9901
12376
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
914
1828
2742
3656
4570
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.0719 AC: 10945AN: 152182Hom.: 444 Cov.: 31 AF XY: 0.0699 AC XY: 5200AN XY: 74400 show subpopulations
GnomAD4 genome
AF:
AC:
10945
AN:
152182
Hom.:
Cov.:
31
AF XY:
AC XY:
5200
AN XY:
74400
Gnomad4 AFR
AF:
AC:
0.0782598
AN:
0.0782598
Gnomad4 AMR
AF:
AC:
0.0739239
AN:
0.0739239
Gnomad4 ASJ
AF:
AC:
0.138279
AN:
0.138279
Gnomad4 EAS
AF:
AC:
0.0283893
AN:
0.0283893
Gnomad4 SAS
AF:
AC:
0.076971
AN:
0.076971
Gnomad4 FIN
AF:
AC:
0.0153397
AN:
0.0153397
Gnomad4 NFE
AF:
AC:
0.0734118
AN:
0.0734118
Gnomad4 OTH
AF:
AC:
0.0946074
AN:
0.0946074
Heterozygous variant carriers
0
509
1018
1528
2037
2546
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
122
244
366
488
610
<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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
202
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
Mutation Taster
=100/0
polymorphism (auto)
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at