Variant rs472093 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000376259.7(TNFRSF1B):c.307+49T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,591,908 control chromosomes in the GnomAD database, including 25,437 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 0.15 ( 1806 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23631 hom. )

Consequence

TNFRSF1B
ENST00000376259.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

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=-0.95).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 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.307+49T>A		intron_variant		ENST00000376259.7	NP_001057.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
TNFRSF1B	ENST00000376259.7 linkuse as main transcript	c.307+49T>A	intron_variant	1	NM_001066.3	ENSP00000365435	P1	P20333-1
TNFRSF1B	ENST00000536782.2 linkuse as main transcript	c.307+49T>A	intron_variant	1		ENSP00000440425
TNFRSF1B	ENST00000492361.1 linkuse as main transcript	n.296+49T>A	intron_variant, non_coding_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22124

AN:

152082

Hom.:

1801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0812

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.153

GnomAD3 exomes

AF:

0.167

AC:

40276

AN:

241524

Hom.:

3623

AF XY:

0.174

AC XY:

22759

AN XY:

130832

show subpopulations

Gnomad AFR exome

AF:

0.0830

Gnomad AMR exome

AF:

0.0982

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.178

AC:

255907

AN:

1439708

Hom.:

23631

Cov.:

AF XY:

0.180

AC XY:

128532

AN XY:

713382

show subpopulations

Gnomad4 AFR exome

AF:

0.0832

Gnomad4 AMR exome

AF:

0.0999

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.228

Gnomad4 FIN exome

AF:

0.157

Gnomad4 NFE exome

AF:

0.181

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.146

AC:

22156

AN:

152200

Hom.:

1806

Cov.:

AF XY:

0.145

AC XY:

10821

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0817

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.169

Hom.:

498

Bravo

AF:

0.139

Asia WGS

AF:

0.157

AC:

550

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.031

DANN

Benign

0.53

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