rs73222599

Variant names:

• chr8-23219776-C-A
• rs73222599
• NM_003844.4:c.306+4980G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003844.4(TNFRSF10A):​c.306+4980G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,036 control chromosomes in the GnomAD database, including 5,614 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 0.27 (5614 hom., cov: 33)
• Consequence: TNFRSF10A NM_003844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4	c.306+4980G>T		intron_variant	Intron 1 of 9	ENST00000221132.8	NP_003835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10A	ENST00000221132.8	c.306+4980G>T		intron_variant	Intron 1 of 9	1	NM_003844.4	ENSP00000221132.3
TNFRSF10A	ENST00000613472.1	c.31+5255G>T		intron_variant	Intron 1 of 8	1		ENSP00000480778.1
TNFRSF10A	ENST00000524158.5	c.-301+4657G>T		intron_variant	Intron 1 of 6	5		ENSP00000428884.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41230 AN: 151918 Hom.: 5605 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.271 AC: 41268 AN: 152036 Hom.: 5614 Cov.: 33 AF XY: 0.274 AC XY: 20402 AN XY: 74336

African (AFR) AF: 0.272 AC: 11284 AN: 41468

American (AMR) AF: 0.342 AC: 5227 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3468

East Asian (EAS) AF: 0.295 AC: 1526 AN: 5172

South Asian (SAS) AF: 0.390 AC: 1881 AN: 4820

European-Finnish (FIN) AF: 0.240 AC: 2533 AN: 10576

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.248 AC: 16848 AN: 67942

Other (OTH) AF: 0.288 AC: 609 AN: 2112

Alfa AF: 0.256 Hom.: 628

Bravo AF: 0.278

Asia WGS AF: 0.331 AC: 1148 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	2.2
DANN	Benign	0.75
PhyloP100		-0.044
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73222599; hg19: chr8-23077289;