rs3924519

chr8-23147116-T-Cchr8-23147116-T-G

Variant summary

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

The NM_003840.5(TNFRSF10D):c.371-44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,539,050 control chromosomes in the GnomAD database, including 89,699 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 0.36 (11006 hom., cov: 31)
  • Exomes 𝑓: 0.32 (78693 hom.)
• Consequence: TNFRSF10D NM_003840.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

Genes affected

TNFRSF10D (HGNC:11907): (TNF receptor superfamily member 10d) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain, a transmembrane domain, and a truncated cytoplamic death domain. This receptor does not induce apoptosis, and has been shown to play an inhibitory role in TRAIL-induced cell apoptosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF10D	NM_003840.5	c.371-44A>G		intron_variant		ENST00000312584.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF10D	ENST00000312584.4	c.371-44A>G		intron_variant		1	NM_003840.5	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54426 AN: 151822 Hom.: 10988 Cov.: 31

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.376

GnomAD3 exomes AF: 0.382 AC: 95255 AN: 249314 Hom.: 21942 AF XY: 0.370 AC XY: 49835 AN XY: 134842

Gnomad AFR exome AF: 0.421

Gnomad AMR exome AF: 0.584

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.827

Gnomad SAS exome AF: 0.373

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.316 AC: 438197 AN: 1387110 Hom.: 78693 Cov.: 20 AF XY: 0.315 AC XY: 219013 AN XY: 694298

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.570

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.835

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.334

GnomAD4 genome AF: 0.359 AC: 54502 AN: 151940 Hom.: 11006 Cov.: 31 AF XY: 0.365 AC XY: 27083 AN XY: 74282

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.378

Alfa AF: 0.296 Hom.: 12830

Bravo AF: 0.382

Asia WGS AF: 0.574 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.14
Dann	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs3924519; hg19: chr8-23004629;