rs73222601

Positions:

• chr8-23222536-A-G

Variant summary

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

The ENST00000221132.8(TNFRSF10A):​c.306+2220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,190 control chromosomes in the GnomAD database, including 4,056 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 (4056 hom., cov: 32)
• Consequence: TNFRSF10A ENST00000221132.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4	c.306+2220T>C		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+2220T>C		intron_variant		1	NM_003844.4	ENSP00000221132	P1
TNFRSF10A	ENST00000613472.1	c.31+2495T>C		intron_variant		1		ENSP00000480778
TNFRSF10A	ENST00000524158.5	c.-301+1897T>C		intron_variant		5		ENSP00000428884

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31834 AN: 152072 Hom.: 4051 Cov.: 32

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.209 AC: 31852 AN: 152190 Hom.: 4056 Cov.: 32 AF XY: 0.214 AC XY: 15891 AN XY: 74398

Gnomad4 AFR AF: 0.0623

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.243

Alfa AF: 0.221 Hom.: 969

Bravo AF: 0.208

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.69
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73222601; hg19: chr8-23080049;