chr8-23030894-G-A

Position:

• chr8-23030894-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003842.5(TNFRSF10B):​c.251-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 1,561,402 control chromosomes in the GnomAD database, including 617,074 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 0.85 (55898 hom., cov: 29)
  • Exomes 𝑓: 0.89 (561176 hom.)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.251-22C>T		intron_variant		ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.251-22C>T		intron_variant			NP_671716.2
TNFRSF10B	NR_027140.2	n.282-22C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.251-22C>T		intron_variant		1	NM_003842.5	ENSP00000276431	P2

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129692 AN: 151814 Hom.: 55862 Cov.: 29

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.850

GnomAD3 exomes AF: 0.890 AC: 198571 AN: 223048 Hom.: 88659 AF XY: 0.891 AC XY: 106861 AN XY: 119892

Gnomad AFR exome AF: 0.741

Gnomad AMR exome AF: 0.884

Gnomad ASJ exome AF: 0.905

Gnomad EAS exome AF: 0.979

Gnomad SAS exome AF: 0.859

Gnomad FIN exome AF: 0.935

Gnomad NFE exome AF: 0.897

Gnomad OTH exome AF: 0.885

GnomAD4 exome AF: 0.892 AC: 1256712 AN: 1409472 Hom.: 561176 Cov.: 21 AF XY: 0.891 AC XY: 625407 AN XY: 701658

Gnomad4 AFR exome AF: 0.730

Gnomad4 AMR exome AF: 0.881

Gnomad4 ASJ exome AF: 0.908

Gnomad4 EAS exome AF: 0.975

Gnomad4 SAS exome AF: 0.858

Gnomad4 FIN exome AF: 0.934

Gnomad4 NFE exome AF: 0.895

Gnomad4 OTH exome AF: 0.884

GnomAD4 genome AF: 0.854 AC: 129788 AN: 151930 Hom.: 55898 Cov.: 29 AF XY: 0.857 AC XY: 63697 AN XY: 74284

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.900

Gnomad4 EAS AF: 0.981

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.935

Gnomad4 NFE AF: 0.895

Gnomad4 OTH AF: 0.851

Alfa AF: 0.885 Hom.: 36148

Bravo AF: 0.844

Asia WGS AF: 0.911 AC: 3166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.5
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10866818; hg19: chr8-22888407;