8-23030095-G-A

Variant names:

• chr8-23030095-G-A
• rs4460370
• NM_003842.5:c.365-374C>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.365-374C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,868 control chromosomes in the GnomAD database, including 7,140 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 0.30 (7140 hom., cov: 31)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	NM_003842.5	MANE Select	c.365-374C>T		intron	N/A	NP_003833.4
	TNFRSF10B	NM_147187.3		c.365-374C>T		intron	N/A	NP_671716.2
	TNFRSF10B	NR_027140.2		n.396-374C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	ENST00000276431.9	TSL:1 MANE Select	c.365-374C>T		intron	N/A	ENSP00000276431.4
	TNFRSF10B	ENST00000347739.3	TSL:1	c.365-374C>T		intron	N/A	ENSP00000317859.3
	TNFRSF10B	ENST00000518531.5	TSL:3	n.115-374C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45887 AN: 151748 Hom.: 7142 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.302 AC: 45900 AN: 151868 Hom.: 7140 Cov.: 31 AF XY: 0.303 AC XY: 22468 AN XY: 74244

African (AFR) AF: 0.229 AC: 9497 AN: 41446

American (AMR) AF: 0.348 AC: 5325 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 922 AN: 3450

East Asian (EAS) AF: 0.352 AC: 1800 AN: 5118

South Asian (SAS) AF: 0.321 AC: 1550 AN: 4822

European-Finnish (FIN) AF: 0.315 AC: 3322 AN: 10560

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22541 AN: 67868

Other (OTH) AF: 0.305 AC: 643 AN: 2106

Alfa AF: 0.315 Hom.: 1142

Bravo AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.73
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs4460370; hg19: chr8-22887608;