chr8-23044358-A-G

Variant names:

• chr8-23044358-A-G
• rs7836280
• NM_003842.5:c.145-1115T>C

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.145-1115T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,112 control chromosomes in the GnomAD database, including 16,284 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 0.42 (16284 hom., cov: 33)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 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.145-1115T>C		intron	N/A	NP_003833.4
	TNFRSF10B	NM_147187.3		c.145-1115T>C		intron	N/A	NP_671716.2
	TNFRSF10B	NR_027140.2		n.282-13486T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	ENST00000276431.9	TSL:1 MANE Select	c.145-1115T>C		intron	N/A	ENSP00000276431.4
	TNFRSF10B	ENST00000347739.3	TSL:1	c.145-1115T>C		intron	N/A	ENSP00000317859.3
	TNFRSF10B	ENST00000519028.1	TSL:2	n.273-1115T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64302 AN: 151994 Hom.: 16249 Cov.: 33

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.423 AC: 64388 AN: 152112 Hom.: 16284 Cov.: 33 AF XY: 0.419 AC XY: 31176 AN XY: 74368

African (AFR) AF: 0.708 AC: 29361 AN: 41486

American (AMR) AF: 0.279 AC: 4266 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1425 AN: 5182

South Asian (SAS) AF: 0.245 AC: 1183 AN: 4822

European-Finnish (FIN) AF: 0.368 AC: 3883 AN: 10552

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21806 AN: 67984

Other (OTH) AF: 0.401 AC: 849 AN: 2116

Alfa AF: 0.302 Hom.: 1489

Bravo AF: 0.428

Asia WGS AF: 0.292 AC: 1015 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.057
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: rs7836280; hg19: chr8-22901871;