rs2235126

chr8-23199668-C-T

Variant summary

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

The NM_003844.4(TNFRSF10A):c.831+218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,026 control chromosomes in the GnomAD database, including 6,059 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 0.26 (6059 hom., cov: 32)
• Consequence: TNFRSF10A NM_003844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.880

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF10A	NM_003844.4	c.831+218G>A		intron_variant		ENST00000221132.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF10A	ENST00000221132.8	c.831+218G>A		intron_variant		1	NM_003844.4	P1
TNFRSF10A	ENST00000613472.1	c.357+218G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40003 AN: 151908 Hom.: 6054 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.263 AC: 40040 AN: 152026 Hom.: 6059 Cov.: 32 AF XY: 0.265 AC XY: 19687 AN XY: 74312

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.291

Alfa AF: 0.272 Hom.: 7682

Bravo AF: 0.272

Asia WGS AF: 0.448 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.6
Dann	Benign	0.43

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: rs2235126; hg19: chr8-23057181;