8-23037252-T-C

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.250+5886A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,890 control chromosomes in the GnomAD database, including 7,544 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 0.31 ( 7544 hom., cov: 31)

Consequence

TNFRSF10B
NM_003842.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.273
Variant links:
Genes affected
TNFRSF10B (HGNC:11905): (TNF receptor superfamily member 10b) The protein encoded by this gene is a member of the TNF-receptor superfamily, and contains an intracellular death domain. This receptor can be activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL/APO-2L), and transduces an apoptosis signal. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for this gene. [provided by RefSeq, Mar 2009]

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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=-0.87).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNFRSF10BNM_003842.5 linkuse as main transcriptc.250+5886A>G intron_variant ENST00000276431.9 NP_003833.4 O14763-1Q7Z2I8
TNFRSF10BNM_147187.3 linkuse as main transcriptc.250+5886A>G intron_variant NP_671716.2 O14763-2
TNFRSF10BNR_027140.2 linkuse as main transcriptn.282-6380A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TNFRSF10BENST00000276431.9 linkuse as main transcriptc.250+5886A>G intron_variant 1 NM_003842.5 ENSP00000276431.4 O14763-1
TNFRSF10BENST00000347739.3 linkuse as main transcriptc.250+5886A>G intron_variant 1 ENSP00000317859.3 O14763-2
TNFRSF10BENST00000519910.1 linkuse as main transcriptn.257+5886A>G intron_variant 4
TNFRSF10BENST00000523504.5 linkuse as main transcriptn.145-6380A>G intron_variant 2 ENSP00000427999.1 E9PBT3

Frequencies

GnomAD3 genomes
AF:
0.312
AC:
47290
AN:
151772
Hom.:
7543
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.246
Gnomad AMI
AF:
0.235
Gnomad AMR
AF:
0.354
Gnomad ASJ
AF:
0.270
Gnomad EAS
AF:
0.359
Gnomad SAS
AF:
0.330
Gnomad FIN
AF:
0.324
Gnomad MID
AF:
0.309
Gnomad NFE
AF:
0.338
Gnomad OTH
AF:
0.315
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.311
AC:
47311
AN:
151890
Hom.:
7544
Cov.:
31
AF XY:
0.312
AC XY:
23154
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.246
Gnomad4 AMR
AF:
0.353
Gnomad4 ASJ
AF:
0.270
Gnomad4 EAS
AF:
0.359
Gnomad4 SAS
AF:
0.331
Gnomad4 FIN
AF:
0.324
Gnomad4 NFE
AF:
0.338
Gnomad4 OTH
AF:
0.312
Alfa
AF:
0.314
Hom.:
1441
Bravo
AF:
0.311
Asia WGS
AF:
0.327
AC:
1136
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
4.4
DANN
Benign
0.74

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.

Other links and lift over

dbSNP: rs12541497; hg19: chr8-22894765; API