rs4872088

Positions:

• chr8-23218667-G-A
• chr8-23218667-G-C

Variant summary

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

The NM_003844.4(TNFRSF10A):​c.306+6089C>T 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 151,950 control chromosomes in the GnomAD database, including 4,125 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 (4125 hom., cov: 31)
• Consequence: TNFRSF10A NM_003844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4	c.306+6089C>T		intron_variant		ENST00000221132.8	NP_003835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF10A	ENST00000221132.8	c.306+6089C>T		intron_variant		1	NM_003844.4	ENSP00000221132	P1
TNFRSF10A	ENST00000613472.1	c.31+6364C>T		intron_variant		1		ENSP00000480778
TNFRSF10A	ENST00000524158.5	c.-301+5766C>T		intron_variant		5		ENSP00000428884

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34338 AN: 151832 Hom.: 4120 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.369

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: 34368 AN: 151950 Hom.: 4125 Cov.: 31 AF XY: 0.229 AC XY: 17027 AN XY: 74244

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.243

Alfa AF: 0.226 Hom.: 830

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	-0.89
CADD	Benign	4.3
DANN	Benign	0.31

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: rs4872088; hg19: chr8-23076180;