NM_003844.4:c.1088-1959G>A

Variant names:

• chr8-23193972-C-T
• rs11775256
• NM_003844.4:c.1088-1959G>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.1088-1959G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,010 control chromosomes in the GnomAD database, including 3,700 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 (3700 hom., cov: 32)
• Consequence: TNFRSF10A NM_003844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 15 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 (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4	c.1088-1959G>A		intron_variant	Intron 9 of 9	ENST00000221132.8	NP_003835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10A	ENST00000221132.8	c.1088-1959G>A		intron_variant	Intron 9 of 9	1	NM_003844.4	ENSP00000221132.3
TNFRSF10A	ENST00000613472.1	c.614-1959G>A		intron_variant	Intron 8 of 8	1		ENSP00000480778.1
TNFRSF10A	ENST00000519862.1	n.143-1959G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31930 AN: 151892 Hom.: 3704 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.210 AC: 31936 AN: 152010 Hom.: 3700 Cov.: 32 AF XY: 0.206 AC XY: 15304 AN XY: 74318

African (AFR) AF: 0.136 AC: 5632 AN: 41498

American (AMR) AF: 0.207 AC: 3156 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3470

East Asian (EAS) AF: 0.0544 AC: 282 AN: 5188

South Asian (SAS) AF: 0.155 AC: 746 AN: 4810

European-Finnish (FIN) AF: 0.232 AC: 2449 AN: 10542

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18049 AN: 67924

Other (OTH) AF: 0.204 AC: 432 AN: 2114

Alfa AF: 0.239 Hom.: 11509

Bravo AF: 0.205

Asia WGS AF: 0.112 AC: 392 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	6.0
DANN	Benign	0.75
PhyloP100		0.14
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: rs11775256; hg19: chr8-23051485;