rs1001793

Variant names:

• chr8-23043436-C-T
• rs1001793
• NM_003842.5:c.145-193G>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.145-193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,022 control chromosomes in the GnomAD database, including 15,624 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 0.41 (15624 hom., cov: 32)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 14 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.145-193G>A		intron_variant	Intron 1 of 8	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.145-193G>A		intron_variant	Intron 1 of 9		NP_671716.2
TNFRSF10B	NR_027140.2	n.282-12564G>A		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.145-193G>A		intron_variant	Intron 1 of 8	1	NM_003842.5	ENSP00000276431.4

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62512 AN: 151904 Hom.: 15590 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.412 AC: 62599 AN: 152022 Hom.: 15624 Cov.: 32 AF XY: 0.408 AC XY: 30323 AN XY: 74306

African (AFR) AF: 0.704 AC: 29156 AN: 41444

American (AMR) AF: 0.271 AC: 4143 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1233 AN: 3466

East Asian (EAS) AF: 0.274 AC: 1415 AN: 5168

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4826

European-Finnish (FIN) AF: 0.358 AC: 3781 AN: 10550

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20535 AN: 67958

Other (OTH) AF: 0.389 AC: 822 AN: 2112

Alfa AF: 0.329 Hom.: 11907

Bravo AF: 0.417

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.7
DANN	Benign	0.72
PhyloP100		-0.088
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: rs1001793; hg19: chr8-22900949;