Variant rs5746016 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.179-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 1,603,760 control chromosomes in the GnomAD database, including 1,979 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 0.041 ( 149 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1830 hom. )

Consequence

TNFRSF1B
NM_001066.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.70

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

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3 link	c.179-35C>T		intron_variant		ENST00000376259.7	NP_001057.1	P20333-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
TNFRSF1B	ENST00000376259.7 link	c.179-35C>T	intron_variant	1	NM_001066.3	ENSP00000365435.3	P20333-1
TNFRSF1B	ENST00000536782.2 link	c.179-35C>T	intron_variant	1		ENSP00000440425.1	B5A977
TNFRSF1B	ENST00000492361.1 link	n.168-35C>T	intron_variant	1

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6308

AN:

151998

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0297

Gnomad FIN

AF:

0.0837

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0503

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0432

AC:

10689

AN:

247478

Hom.:

287

AF XY:

0.0436

AC XY:

5823

AN XY:

133664

show subpopulations

Gnomad AFR exome

AF:

0.0261

Gnomad AMR exome

AF:

0.0202

Gnomad ASJ exome

AF:

0.0600

Gnomad EAS exome

AF:

0.000599

Gnomad SAS exome

AF:

0.0302

Gnomad FIN exome

AF:

0.0811

Gnomad NFE exome

AF:

0.0542

Gnomad OTH exome

AF:

0.0480

GnomAD4 exome

AF:

0.0477

AC:

69226

AN:

1451644

Hom.:

1830

Cov.:

AF XY:

0.0471

AC XY:

33945

AN XY:

720506

show subpopulations

Gnomad4 AFR exome

AF:

0.0281

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.0588

Gnomad4 EAS exome

AF:

0.000329

Gnomad4 SAS exome

AF:

0.0278

Gnomad4 FIN exome

AF:

0.0844

Gnomad4 NFE exome

AF:

0.0509

Gnomad4 OTH exome

AF:

0.0424

GnomAD4 genome

AF:

0.0414

AC:

6304

AN:

152116

Hom.:

149

Cov.:

AF XY:

0.0419

AC XY:

3113

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0256

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.0565

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0293

Gnomad4 FIN

AF:

0.0837

Gnomad4 NFE

AF:

0.0503

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0479

Hom.:

122

Bravo

AF:

0.0364

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.1

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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