8-23193972-C-T

Position:

• chr8-23193972-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.1088-1959G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,010 control chromosomes in the GnomAD database, including 3,700 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 0.21 (3700 hom., cov: 32)
• Consequence: TNFRSF10A NM_003844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF10A	NM_003844.4	c.1088-1959G>A		intron_variant		ENST00000221132.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF10A	ENST00000221132.8	c.1088-1959G>A		intron_variant		1	NM_003844.4	P1
TNFRSF10A	ENST00000613472.1	c.614-1959G>A		intron_variant		1
TNFRSF10A	ENST00000519862.1	n.143-1959G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31930 AN: 151892 Hom.: 3704 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.210 AC: 31936 AN: 152010 Hom.: 3700 Cov.: 32 AF XY: 0.206 AC XY: 15304 AN XY: 74318

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.0544

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.204

Alfa AF: 0.249 Hom.: 8634

Bravo AF: 0.205

Asia WGS AF: 0.112 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.0
DANN	Benign	0.75

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: rs11775256; hg19: chr8-23051485;