rs4259415

Variant names:

• chr8-23044055-A-C
• rs4259415
• NM_003842.5:c.145-812T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-23044055-A-C
• chr8-23044055-A-G
• chr8-23044055-A-T

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.145-812T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,108 control chromosomes in the GnomAD database, including 30,475 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 0.61 (30475 hom., cov: 33)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 9 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, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 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.145-812T>G		intron	N/A	NP_003833.4
	TNFRSF10B	NM_147187.3		c.145-812T>G		intron	N/A	NP_671716.2	O14763-2
	TNFRSF10B	NR_027140.2		n.282-13183T>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.145-812T>G		intron	N/A	ENSP00000276431.4	O14763-1
	TNFRSF10B	ENST00000347739.3	TSL:1	c.145-812T>G		intron	N/A	ENSP00000317859.3	O14763-2
	TNFRSF10B	ENST00000931215.1		c.145-812T>G		intron	N/A	ENSP00000601274.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92541 AN: 151990 Hom.: 30425 Cov.: 33

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.609 AC: 92655 AN: 152108 Hom.: 30475 Cov.: 33 AF XY: 0.611 AC XY: 45441 AN XY: 74346

African (AFR) AF: 0.861 AC: 35736 AN: 41514

American (AMR) AF: 0.612 AC: 9344 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1845 AN: 3468

East Asian (EAS) AF: 0.750 AC: 3880 AN: 5176

South Asian (SAS) AF: 0.466 AC: 2245 AN: 4822

European-Finnish (FIN) AF: 0.552 AC: 5827 AN: 10562

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.469 AC: 31853 AN: 67980

Other (OTH) AF: 0.594 AC: 1254 AN: 2110

Alfa AF: 0.531 Hom.: 60380

Bravo AF: 0.628

Asia WGS AF: 0.593 AC: 2059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.51
PhyloP100		-0.039
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: rs4259415;

hg19: chr8-22901568;