8-23020813-G-C

Position:

• chr8-23020813-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.*1858C>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 0.0484 in 454,124 control chromosomes in the GnomAD database, including 668 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 0.041 (182 hom., cov: 32)
  • Exomes 𝑓: 0.052 (486 hom.)
• Consequence: TNFRSF10B NM_003842.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.*1858C>G		3_prime_UTR_variant	9/9	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.*1858C>G		3_prime_UTR_variant	10/10		NP_671716.2
TNFRSF10B	NR_027140.2	n.3125C>G		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431	c.*1858C>G		3_prime_UTR_variant	9/9	1	NM_003842.5	ENSP00000276431.4
TNFRSF10B	ENST00000523752.5	n.2648C>G		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6314 AN: 152204 Hom.: 181 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.0430

GnomAD3 exomes AF: 0.0443 AC: 5781 AN: 130506 Hom.: 167 AF XY: 0.0464 AC XY: 3307 AN XY: 71234

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.0224

Gnomad ASJ exome AF: 0.0684

Gnomad EAS exome AF: 0.0000959

Gnomad SAS exome AF: 0.0458

Gnomad FIN exome AF: 0.0708

Gnomad NFE exome AF: 0.0602

Gnomad OTH exome AF: 0.0539

GnomAD4 exome AF: 0.0518 AC: 15648 AN: 301802 Hom.: 486 Cov.: 0 AF XY: 0.0520 AC XY: 8943 AN XY: 171998

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.0227

Gnomad4 ASJ exome AF: 0.0668

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0472

Gnomad4 FIN exome AF: 0.0733

Gnomad4 NFE exome AF: 0.0608

Gnomad4 OTH exome AF: 0.0531

GnomAD4 genome AF: 0.0415 AC: 6315 AN: 152322 Hom.: 182 Cov.: 32 AF XY: 0.0416 AC XY: 3100 AN XY: 74466

Gnomad4 AFR AF: 0.0100

Gnomad4 AMR AF: 0.0309

Gnomad4 ASJ AF: 0.0694

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0431

Gnomad4 FIN AF: 0.0762

Gnomad4 NFE AF: 0.0591

Gnomad4 OTH AF: 0.0425

Alfa AF: 0.0305 Hom.: 19

Bravo AF: 0.0364

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.67

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: rs35974498; hg19: chr8-22878326;