rs1001792

Variant names:

• chr8-23043689-T-C
• rs1001792
• NM_003842.5:c.145-446A>G

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.145-446A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,974 control chromosomes in the GnomAD database, including 16,692 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 0.43 (16692 hom., cov: 32)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 6 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: AR, AD, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003842.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	NM_003842.5	MANE Select	c.145-446A>G		intron	N/A	NP_003833.4
	TNFRSF10B	NM_147187.3		c.145-446A>G		intron	N/A	NP_671716.2	O14763-2
	TNFRSF10B	NR_027140.2		n.282-12817A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	ENST00000276431.9	TSL:1 MANE Select	c.145-446A>G		intron	N/A	ENSP00000276431.4	O14763-1
	TNFRSF10B	ENST00000347739.3	TSL:1	c.145-446A>G		intron	N/A	ENSP00000317859.3	O14763-2
	TNFRSF10B	ENST00000931215.1		c.145-446A>G		intron	N/A	ENSP00000601274.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64899 AN: 151856 Hom.: 16657 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.428 AC: 64984 AN: 151974 Hom.: 16692 Cov.: 32 AF XY: 0.424 AC XY: 31456 AN XY: 74272

African (AFR) AF: 0.721 AC: 29908 AN: 41454

American (AMR) AF: 0.282 AC: 4302 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1245 AN: 3462

East Asian (EAS) AF: 0.274 AC: 1414 AN: 5160

South Asian (SAS) AF: 0.246 AC: 1186 AN: 4820

European-Finnish (FIN) AF: 0.369 AC: 3893 AN: 10550

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

European-Non Finnish (NFE) AF: 0.321 AC: 21818 AN: 67958

Other (OTH) AF: 0.404 AC: 852 AN: 2110

Alfa AF: 0.350 Hom.: 41381

Bravo AF: 0.432

Asia WGS AF: 0.293 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.62
PhyloP100		1.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1001792;

hg19: chr8-22901202;