NM_003810.4:c.271-1135C>T

Variant names:

• chr3-172512794-G-A
• rs3136594
• NM_003810.4:c.271-1135C>T

Variant summary

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

The NM_003810.4(TNFSF10):​c.271-1135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,194 control chromosomes in the GnomAD database, including 4,739 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 0.24 (4739 hom., cov: 33)
• Consequence: TNFSF10 NM_003810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 21 publications found

Genes affected

TNFSF10 (HGNC:11925): (TNF superfamily member 10) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF10	NM_003810.4	c.271-1135C>T		intron_variant	Intron 2 of 4	ENST00000241261.7	NP_003801.1
TNFSF10	NM_001190942.2	c.270+2067C>T		intron_variant	Intron 2 of 2		NP_001177871.1
TNFSF10	NR_033994.2	n.316+2067C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7	c.271-1135C>T		intron_variant	Intron 2 of 4	1	NM_003810.4	ENSP00000241261.2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36606 AN: 152076 Hom.: 4740 Cov.: 33

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.241 AC: 36617 AN: 152194 Hom.: 4739 Cov.: 33 AF XY: 0.243 AC XY: 18044 AN XY: 74400

African (AFR) AF: 0.184 AC: 7642 AN: 41534

American (AMR) AF: 0.211 AC: 3225 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1391 AN: 3468

East Asian (EAS) AF: 0.125 AC: 650 AN: 5186

South Asian (SAS) AF: 0.195 AC: 942 AN: 4826

European-Finnish (FIN) AF: 0.308 AC: 3261 AN: 10588

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18457 AN: 67990

Other (OTH) AF: 0.264 AC: 557 AN: 2106

Alfa AF: 0.263 Hom.: 4134

Bravo AF: 0.231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.69
PhyloP100		-0.61
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: rs3136594; hg19: chr3-172230584;