rs11780345

Positions:

• chr8-23194453-T-C

Variant summary

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

The NM_003844.4(TNFRSF10A):​c.1088-2440A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,240 control chromosomes in the GnomAD database, including 6,665 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 0.28 (6665 hom., cov: 33)
• Consequence: TNFRSF10A NM_003844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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 (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4	c.1088-2440A>G		intron_variant		ENST00000221132.8	NP_003835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF10A	ENST00000221132.8	c.1088-2440A>G		intron_variant		1	NM_003844.4	ENSP00000221132	P1
TNFRSF10A	ENST00000613472.1	c.614-2440A>G		intron_variant		1		ENSP00000480778
TNFRSF10A	ENST00000519862.1	n.143-2440A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42420 AN: 152122 Hom.: 6670 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.279 AC: 42422 AN: 152240 Hom.: 6665 Cov.: 33 AF XY: 0.276 AC XY: 20553 AN XY: 74438

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.265

Alfa AF: 0.338 Hom.: 4708

Bravo AF: 0.265

Asia WGS AF: 0.165 AC: 575 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.0
DANN	Benign	0.73

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: rs11780345; hg19: chr8-23051966;