8-23204120-T-C

Variant names:

• chr8-23204120-T-C
• rs4242392
• NM_003844.4:c.404-1359A>G

Variant summary

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

The NM_003844.4(TNFRSF10A):​c.404-1359A>G 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 151,718 control chromosomes in the GnomAD database, including 3,543 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 (3543 hom., cov: 30)
• Consequence: TNFRSF10A NM_003844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• Publications: 16 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=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4	c.404-1359A>G		intron_variant	Intron 2 of 9	ENST00000221132.8	NP_003835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10A	ENST00000221132.8	c.404-1359A>G		intron_variant	Intron 2 of 9	1	NM_003844.4	ENSP00000221132.3
TNFRSF10A	ENST00000613472.1	c.32-1461A>G		intron_variant	Intron 1 of 8	1		ENSP00000480778.1
TNFRSF10A	ENST00000524158.5	c.-203-1359A>G		intron_variant	Intron 2 of 6	5		ENSP00000428884.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29750 AN: 151598 Hom.: 3540 Cov.: 30

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.196 AC: 29763 AN: 151718 Hom.: 3543 Cov.: 30 AF XY: 0.201 AC XY: 14870 AN XY: 74126

African (AFR) AF: 0.0600 AC: 2483 AN: 41354

American (AMR) AF: 0.304 AC: 4633 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 936 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1558 AN: 5122

South Asian (SAS) AF: 0.366 AC: 1756 AN: 4804

European-Finnish (FIN) AF: 0.204 AC: 2156 AN: 10554

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.228 AC: 15473 AN: 67878

Other (OTH) AF: 0.220 AC: 463 AN: 2104

Alfa AF: 0.197 Hom.: 2557

Bravo AF: 0.195

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.19
PhyloP100		-0.98
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: rs4242392; hg19: chr8-23061633;