8-23040709-G-T

Position:

• chr8-23040709-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.250+2429C>A		intron_variant		ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.250+2429C>A		intron_variant			NP_671716.2
TNFRSF10B	NR_027140.2	n.282-9837C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.250+2429C>A		intron_variant		1	NM_003842.5	ENSP00000276431.4
TNFRSF10B	ENST00000347739.3	c.250+2429C>A		intron_variant		1		ENSP00000317859.3
TNFRSF10B	ENST00000519910.1	n.257+2429C>A		intron_variant		4
TNFRSF10B	ENST00000523504.5	n.145-9837C>A		intron_variant		2		ENSP00000427999.1

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

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.798

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.837

Alfa AF: 0.829 Hom.: 12588

Bravo AF: 0.836

Asia WGS AF: 0.912 AC: 3163 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.63

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: rs4872046; hg19: chr8-22898222;