Variant rs3397 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001066.3(TNFRSF1B):c.*215C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 473,266 control chromosomes in the GnomAD database, including 81,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.51 ( 22516 hom., cov: 33)

Exomes 𝑓: 0.60 ( 59315 hom. )

Consequence

TNFRSF1B
NM_001066.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:3

Conservation

PhyloP100: -0.400

Variant links:

Genes affected

TNFRSF1B (HGNC:11917): (TNF receptor superfamily member 1B) The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein and TNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Knockout studies in mice also suggest a role of this protein in protecting neurons from apoptosis by stimulating antioxidative pathways. [provided by RefSeq, Jul 2008]

TNFRSF1B 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=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3 linkuse as main transcript	c.*215C>T		3_prime_UTR_variant	10/10	ENST00000376259.7	NP_001057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF1B	ENST00000376259.7 linkuse as main transcript	c.*215C>T		3_prime_UTR_variant	10/10	1	NM_001066.3	ENSP00000365435	P1	P20333-1
TNFRSF1B	ENST00000492361.1 linkuse as main transcript	n.1590C>T		non_coding_transcript_exon_variant	9/9	1

Frequencies

GnomAD3 genomes

AF:

0.510

AC:

77531

AN:

152072

Hom.:

22512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.667

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.623

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.535

GnomAD4 exome

AF:

0.599

AC:

192198

AN:

321076

Hom.:

59315

Cov.:

AF XY:

0.600

AC XY:

98421

AN XY:

163988

show subpopulations

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.703

Gnomad4 ASJ exome

AF:

0.670

Gnomad4 EAS exome

AF:

0.343

Gnomad4 SAS exome

AF:

0.478

Gnomad4 FIN exome

AF:

0.608

Gnomad4 NFE exome

AF:

0.643

Gnomad4 OTH exome

AF:

0.576

GnomAD4 genome

AF:

0.510

AC:

77556

AN:

152190

Hom.:

22516

Cov.:

AF XY:

0.511

AC XY:

38008

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.673

Gnomad4 ASJ

AF:

0.667

Gnomad4 EAS

AF:

0.306

Gnomad4 SAS

AF:

0.432

Gnomad4 FIN

AF:

0.623

Gnomad4 NFE

AF:

0.640

Gnomad4 OTH

AF:

0.531

Alfa

AF:

0.583

Hom.:

8581

Bravo

AF:

0.506

Asia WGS

AF:

0.340

AC:

1183

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Associated with severe COVID-19 disease

Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 01, 2023

- -

Susceptibility to severe coronavirus disease (COVID-19)

Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Feb 09, 2021

- -

Susceptibility to severe coronavirus disease (COVID-19) due to high plasma levels of TNF, TNFR, and/or TNFR3

Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Aug 07, 2021

Differences in PaO2/FiO2 levels in patients with severe COVID-19 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.5

DANN

Benign

0.86

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over