rs73222600

Variant names:

• chr8-23219777-A-G
• rs73222600
• NM_003844.4:c.306+4979T>C

Variant summary

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

The ENST00000221132.8(TNFRSF10A):​c.306+4979T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,042 control chromosomes in the GnomAD database, including 5,645 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 (5645 hom., cov: 33)
• Consequence: TNFRSF10A ENST00000221132.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000221132.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10A	NM_003844.4	MANE Select	c.306+4979T>C		intron	N/A	NP_003835.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10A	ENST00000221132.8	TSL:1 MANE Select	c.306+4979T>C		intron	N/A	ENSP00000221132.3
	TNFRSF10A	ENST00000613472.1	TSL:1	c.31+5254T>C		intron	N/A	ENSP00000480778.1
	TNFRSF10A	ENST00000524158.5	TSL:5	c.-301+4656T>C		intron	N/A	ENSP00000428884.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41308 AN: 151924 Hom.: 5636 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.272 AC: 41345 AN: 152042 Hom.: 5645 Cov.: 33 AF XY: 0.275 AC XY: 20440 AN XY: 74340

African (AFR) AF: 0.273 AC: 11336 AN: 41484

American (AMR) AF: 0.342 AC: 5229 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1028 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1539 AN: 5166

South Asian (SAS) AF: 0.390 AC: 1882 AN: 4820

European-Finnish (FIN) AF: 0.240 AC: 2534 AN: 10578

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

European-Non Finnish (NFE) AF: 0.248 AC: 16853 AN: 67934

Other (OTH) AF: 0.289 AC: 610 AN: 2114

Alfa AF: 0.256 Hom.: 1727

Bravo AF: 0.278

Asia WGS AF: 0.331 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.55
PhyloP100		-1.5
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: rs73222600; hg19: chr8-23077290;