chr8-23040709-G-T

Variant names:

• chr8-23040709-G-T
• rs4872046
• NM_003842.5:c.250+2429C>A

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.250+2429C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 151,752 control chromosomes in the GnomAD database, including 52,895 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 0.83 (52895 hom., cov: 31)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 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.250+2429C>A		intron	N/A	NP_003833.4
	TNFRSF10B	NM_147187.3		c.250+2429C>A		intron	N/A	NP_671716.2
	TNFRSF10B	NR_027140.2		n.282-9837C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	ENST00000276431.9	TSL:1 MANE Select	c.250+2429C>A		intron	N/A	ENSP00000276431.4
	TNFRSF10B	ENST00000347739.3	TSL:1	c.250+2429C>A		intron	N/A	ENSP00000317859.3
	TNFRSF10B	ENST00000931215.1		c.250+2429C>A		intron	N/A	ENSP00000601274.1

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126472 AN: 151636 Hom.: 52835 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.834 AC: 126589 AN: 151752 Hom.: 52895 Cov.: 31 AF XY: 0.835 AC XY: 61935 AN XY: 74146

African (AFR) AF: 0.812 AC: 33588 AN: 41388

American (AMR) AF: 0.878 AC: 13384 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2768 AN: 3468

East Asian (EAS) AF: 0.949 AC: 4923 AN: 5186

South Asian (SAS) AF: 0.869 AC: 4192 AN: 4824

European-Finnish (FIN) AF: 0.815 AC: 8466 AN: 10392

Middle Eastern (MID) AF: 0.812 AC: 237 AN: 292

European-Non Finnish (NFE) AF: 0.831 AC: 56444 AN: 67936

Other (OTH) AF: 0.837 AC: 1761 AN: 2104

Alfa AF: 0.832 Hom.: 84629

Bravo AF: 0.836

Asia WGS AF: 0.912 AC: 3163 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-0.079
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: rs4872046; hg19: chr8-22898222;