rs1001792

Positions:

• chr8-23043689-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.145-446A>G		intron_variant		ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.145-446A>G		intron_variant			NP_671716.2
TNFRSF10B	NR_027140.2	n.282-12817A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.145-446A>G		intron_variant		1	NM_003842.5	ENSP00000276431.4

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

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.404

Alfa AF: 0.331 Hom.: 15215

Bravo AF: 0.432

Asia WGS AF: 0.293 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Other links and lift over

dbSNP: rs1001792; hg19: chr8-22901202;