8-23217806-C-T

Variant names:

• chr8-23217806-C-T
• rs73222596
• NM_003844.4:c.307-5594G>A

Variant summary

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

The NM_003844.4(TNFRSF10A):​c.307-5594G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,146 control chromosomes in the GnomAD database, including 3,553 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 0.20 (3553 hom., cov: 32)
• Consequence: TNFRSF10A NM_003844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4	c.307-5594G>A		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.307-5594G>A		intron_variant	Intron 1 of 9	1	NM_003844.4	ENSP00000221132.3
TNFRSF10A	ENST00000613472.1	c.31+7225G>A		intron_variant	Intron 1 of 8	1		ENSP00000480778.1
TNFRSF10A	ENST00000524158.5	c.-300-5594G>A		intron_variant	Intron 1 of 6	5		ENSP00000428884.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29755 AN: 152026 Hom.: 3550 Cov.: 32

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.196 AC: 29767 AN: 152146 Hom.: 3553 Cov.: 32 AF XY: 0.200 AC XY: 14892 AN XY: 74366

African (AFR) AF: 0.0595 AC: 2470 AN: 41538

American (AMR) AF: 0.309 AC: 4723 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3472

East Asian (EAS) AF: 0.298 AC: 1537 AN: 5154

South Asian (SAS) AF: 0.360 AC: 1731 AN: 4806

European-Finnish (FIN) AF: 0.205 AC: 2170 AN: 10584

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15442 AN: 67992

Other (OTH) AF: 0.218 AC: 461 AN: 2112

Alfa AF: 0.107 Hom.: 179

Bravo AF: 0.195

Asia WGS AF: 0.314 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.67
PhyloP100		-3.0
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: rs73222596; hg19: chr8-23075319;