8-23022649-G-C

Position:

• chr8-23022649-G-C

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.*22C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,613,034 control chromosomes in the GnomAD database, including 259,189 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 0.49 (19792 hom., cov: 30)
  • Exomes 𝑓: 0.57 (239397 hom.)
• Consequence: TNFRSF10B NM_003842.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.*22C>G		3_prime_UTR_variant	9/9	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.*22C>G		3_prime_UTR_variant	10/10		NP_671716.2
TNFRSF10B	NR_027140.2	n.1289C>G		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431	c.*22C>G		3_prime_UTR_variant	9/9	1	NM_003842.5	ENSP00000276431.4

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74478 AN: 151684 Hom.: 19787 Cov.: 30

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.488

GnomAD3 exomes AF: 0.538 AC: 134893 AN: 250878 Hom.: 37780 AF XY: 0.537 AC XY: 72889 AN XY: 135610

Gnomad AFR exome AF: 0.284

Gnomad AMR exome AF: 0.519

Gnomad ASJ exome AF: 0.642

Gnomad EAS exome AF: 0.464

Gnomad SAS exome AF: 0.413

Gnomad FIN exome AF: 0.690

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.556

GnomAD4 exome AF: 0.568 AC: 829658 AN: 1461232 Hom.: 239397 Cov.: 38 AF XY: 0.565 AC XY: 410373 AN XY: 726924

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.644

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.419

Gnomad4 FIN exome AF: 0.687

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.549

GnomAD4 genome AF: 0.491 AC: 74513 AN: 151802 Hom.: 19792 Cov.: 30 AF XY: 0.493 AC XY: 36588 AN XY: 74180

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.485

Alfa AF: 0.548 Hom.: 4249

Bravo AF: 0.468

Asia WGS AF: 0.405 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.85
DANN	Benign	0.70

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: rs1047275; hg19: chr8-22880162; COSMIC: COSV52391450; COSMIC: COSV52391450;