Variant rs945439 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001066.3(TNFRSF1B):c.168A>G(p.Lys56Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,612,264 control chromosomes in the GnomAD database, including 44,356 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 0.22 ( 3713 hom., cov: 33)

Exomes 𝑓: 0.23 ( 40643 hom. )

Consequence

TNFRSF1B
NM_001066.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.74

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP7

Synonymous conserved (PhyloP=1.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 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.168A>G	p.Lys56Lys	synonymous_variant	2/10	ENST00000376259.7	NP_001057.1	P20333-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TNFRSF1B	ENST00000376259.7 linkuse as main transcript	c.168A>G	p.Lys56Lys	synonymous_variant	2/10	1	NM_001066.3	ENSP00000365435.3	P20333-1
TNFRSF1B	ENST00000536782.2 linkuse as main transcript	c.168A>G	p.Lys56Lys	synonymous_variant	2/5	1		ENSP00000440425.1	B5A977
TNFRSF1B	ENST00000492361.1 linkuse as main transcript	n.168-2072A>G		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33146

AN:

152060

Hom.:

3702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.215

AC:

53808

AN:

249760

Hom.:

6083

AF XY:

0.221

AC XY:

29838

AN XY:

135126

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.158

Gnomad SAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.233

AC:

339913

AN:

1460086

Hom.:

40643

Cov.:

AF XY:

0.234

AC XY:

170043

AN XY:

726282

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.268

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.261

Gnomad4 FIN exome

AF:

0.204

Gnomad4 NFE exome

AF:

0.239

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.218

AC:

33188

AN:

152178

Hom.:

3713

Cov.:

AF XY:

0.215

AC XY:

15982

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.256

Gnomad4 FIN

AF:

0.203

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.232

Hom.:

5510

Bravo

AF:

0.212

Asia WGS

AF:

0.181

AC:

633

AN:

3478

EpiCase

AF:

0.234

EpiControl

AF:

0.236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.5

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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