rs4872089

chr8-23218821-T-G

Variant summary

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

The NM_003844.4(TNFRSF10A):c.306+5935A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,170 control chromosomes in the GnomAD database, including 4,122 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 0.23 (4122 hom., cov: 32)
• Consequence: TNFRSF10A NM_003844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538

Genes affected

TNFRSF10A (HGNC:11904): (TNF receptor superfamily member 10a) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF10A	NM_003844.4	c.306+5935A>C		intron_variant		ENST00000221132.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF10A	ENST00000221132.8	c.306+5935A>C		intron_variant		1	NM_003844.4	P1
TNFRSF10A	ENST00000613472.1	c.31+6210A>C		intron_variant		1
TNFRSF10A	ENST00000524158.5	c.-301+5612A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34423 AN: 152052 Hom.: 4116 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 34455 AN: 152170 Hom.: 4122 Cov.: 32 AF XY: 0.230 AC XY: 17090 AN XY: 74388

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.244

Alfa AF: 0.224 Hom.: 905

Bravo AF: 0.230

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.2
Dann	Benign	0.54

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: rs4872089; hg19: chr8-23076334;