rs883429

Variant names:

• chr8-23029305-C-T
• rs883429
• NM_003842.5:c.476+305G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003842.5(TNFRSF10B):​c.476+305G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,214 control chromosomes in the GnomAD database, including 5,314 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 0.26 (5314 hom., cov: 32)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 7 publications found

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]

TNFRSF10B Gene-Disease associations (from GenCC):

• head and neck squamous cell carcinoma

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.476+305G>A		intron_variant	Intron 4 of 8	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.476+305G>A		intron_variant	Intron 4 of 9		NP_671716.2
TNFRSF10B	NR_027140.2	n.507+305G>A		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.476+305G>A		intron_variant	Intron 4 of 8	1	NM_003842.5	ENSP00000276431.4

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39342 AN: 152096 Hom.: 5314 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.280

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39359 AN: 152214 Hom.: 5314 Cov.: 32 AF XY: 0.260 AC XY: 19328 AN XY: 74448

African (AFR) AF: 0.213 AC: 8829 AN: 41526

American (AMR) AF: 0.329 AC: 5029 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1795 AN: 5172

South Asian (SAS) AF: 0.302 AC: 1460 AN: 4828

European-Finnish (FIN) AF: 0.217 AC: 2303 AN: 10618

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18231 AN: 67982

Other (OTH) AF: 0.277 AC: 586 AN: 2114

Alfa AF: 0.264 Hom.: 3350

Bravo AF: 0.266

Asia WGS AF: 0.309 AC: 1075 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	0.85
DANN	Benign	0.51
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs883429; hg19: chr8-22886818;