Variant rs17883432 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001066.3(TNFRSF1B):c.902C>G(p.Pro301Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,607,616 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00048 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

TNFRSF1B
NM_001066.3 missense, splice_region

Scores

Splicing: ADA: 0.005637

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

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:

TNFRSF1B (HGNC:):

TNFRSF1B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011523366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3 linkuse as main transcript	c.902C>G	p.Pro301Arg	missense_variant, splice_region_variant	9/10	ENST00000376259.7	NP_001057.1	P20333-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF1B	ENST00000376259.7 linkuse as main transcript	c.902C>G	p.Pro301Arg	missense_variant, splice_region_variant	9/10	1	NM_001066.3	ENSP00000365435.3		P20333-1
TNFRSF1B	ENST00000492361.1 linkuse as main transcript	n.891C>G		splice_region_variant, non_coding_transcript_exon_variant	8/9	1

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000300

AC:

AN:

236286

Hom.:

AF XY:

0.000270

AC XY:

AN XY:

129600

show subpopulations

Gnomad AFR exome

AF:

0.000852

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00545

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000285

Gnomad OTH exome

AF:

0.000346

GnomAD4 exome

AF:

0.000153

AC:

222

AN:

1455302

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

723024

show subpopulations

Gnomad4 AFR exome

AF:

0.000899

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00500

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000235

Gnomad4 OTH exome

AF:

0.000483

GnomAD4 genome

AF:

0.000479

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000653

Hom.:

Bravo

AF:

0.000457

ExAC

AF:

0.000281

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.36

Eigen

Benign

-0.049

Eigen_PC

Benign

0.037

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.75

M_CAP

Benign

0.061

MetaRNN

Benign

0.012

MetaSVM

Uncertain

-0.19

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.52

Sift

Benign

0.32

Sift4G

Uncertain

0.0040

Polyphen

0.25

Vest4

0.35

MVP

0.90

MPC

0.49

ClinPred

0.019

GERP RS

5.0

Varity_R

0.11

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0056

dbscSNV1_RF

Benign

0.060

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