Variant rs3093665 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000594.4(TNF):c.*77A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,563,882 control chromosomes in the GnomAD database, including 472 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 0.025 ( 56 hom., cov: 32)

Exomes 𝑓: 0.020 ( 416 hom. )

Consequence

TNF
NM_000594.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.325

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]

TNF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0245 (3738/152280) while in subpopulation AFR AF= 0.0359 (1493/41546). AF 95% confidence interval is 0.0344. There are 56 homozygotes in gnomad4. There are 1723 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3738 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNF	NM_000594.4 linkuse as main transcript	c.*77A>C		3_prime_UTR_variant	4/4	ENST00000449264.3	NP_000585.2	P01375Q5STB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNF	ENST00000449264.3 linkuse as main transcript	c.*77A>C		3_prime_UTR_variant	4/4	1	NM_000594.4	ENSP00000398698.2		P01375

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

3731

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0359

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.0688

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0193

AC:

4245

AN:

219800

Hom.:

AF XY:

0.0197

AC XY:

2368

AN XY:

120314

show subpopulations

Gnomad AFR exome

AF:

0.0369

Gnomad AMR exome

AF:

0.0194

Gnomad ASJ exome

AF:

0.0680

Gnomad EAS exome

AF:

0.000238

Gnomad SAS exome

AF:

0.0110

Gnomad FIN exome

AF:

0.00205

Gnomad NFE exome

AF:

0.0210

Gnomad OTH exome

AF:

0.0242

GnomAD4 exome

AF:

0.0201

AC:

28406

AN:

1411602

Hom.:

416

Cov.:

AF XY:

0.0203

AC XY:

14251

AN XY:

702078

show subpopulations

Gnomad4 AFR exome

AF:

0.0359

Gnomad4 AMR exome

AF:

0.0210

Gnomad4 ASJ exome

AF:

0.0701

Gnomad4 EAS exome

AF:

0.000204

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.00271

Gnomad4 NFE exome

AF:

0.0200

Gnomad4 OTH exome

AF:

0.0289

GnomAD4 genome

AF:

0.0245

AC:

3738

AN:

152280

Hom.:

Cov.:

AF XY:

0.0231

AC XY:

1723

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0359

Gnomad4 AMR

AF:

0.0235

Gnomad4 ASJ

AF:

0.0688

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.0212

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0263

Hom.:

120

Bravo

AF:

0.0275

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.5

DANN

Benign

0.72

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over