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6-31575828-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000594.4(TNF):c.87G>T(p.Arg29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,612,698 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 51 hom., cov: 31)
Exomes 𝑓: 0.0016 ( 54 hom. )

Consequence

TNF
NM_000594.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.641
Variant links:
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 made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-31575828-G-T is Benign according to our data. Variant chr6-31575828-G-T is described in ClinVar as [Benign]. Clinvar id is 784495.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.641 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TNFNM_000594.4 linkuse as main transcriptc.87G>T p.Arg29= synonymous_variant 1/4 ENST00000449264.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNFENST00000449264.3 linkuse as main transcriptc.87G>T p.Arg29= synonymous_variant 1/41 NM_000594.4 P1
TNFENST00000699334.1 linkuse as main transcriptc.87G>T p.Arg29= synonymous_variant 1/3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0151
AC:
2299
AN:
152162
Hom.:
52
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0522
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.0139
GnomAD3 exomes
AF:
0.00401
AC:
1001
AN:
249700
Hom.:
30
AF XY:
0.00325
AC XY:
439
AN XY:
135108
show subpopulations
Gnomad AFR exome
AF:
0.0524
Gnomad AMR exome
AF:
0.00300
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000689
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000159
Gnomad OTH exome
AF:
0.00215
GnomAD4 exome
AF:
0.00160
AC:
2333
AN:
1460418
Hom.:
54
Cov.:
30
AF XY:
0.00138
AC XY:
1000
AN XY:
726580
show subpopulations
Gnomad4 AFR exome
AF:
0.0539
Gnomad4 AMR exome
AF:
0.00341
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000604
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.00413
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0151
AC:
2298
AN:
152280
Hom.:
51
Cov.:
31
AF XY:
0.0150
AC XY:
1116
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0520
Gnomad4 AMR
AF:
0.00588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.00228
Hom.:
14
Bravo
AF:
0.0173
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000596

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 submitterclinical testingInvitaeAug 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
Cadd
Benign
1.1
Dann
Benign
0.81

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: rs2228088; hg19: chr6-31543605; API