3-172508291-G-A

Position:

• chr3-172508291-G-A

Variant summary

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

The NM_003810.4(TNFSF10):​c.418+926C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 132,748 control chromosomes in the GnomAD database, including 3,352 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 0.23 (3352 hom., cov: 30)
• Consequence: TNFSF10 NM_003810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF10	NM_003810.4	c.418+926C>T		intron_variant		ENST00000241261.7
TNFSF10	NM_001190942.2	c.271-1372C>T		intron_variant
TNFSF10	NR_033994.2	n.421+926C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF10	ENST00000241261.7	c.418+926C>T		intron_variant		1	NM_003810.4	P1
TNFSF10	ENST00000420541.6	c.271-1372C>T		intron_variant		1
TNFSF10	ENST00000430881.1	c.*79-842C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 29945 AN: 132644 Hom.: 3353 Cov.: 30

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.438

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.226 AC: 29948 AN: 132748 Hom.: 3352 Cov.: 30 AF XY: 0.228 AC XY: 14714 AN XY: 64420

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.258

Alfa AF: 0.106 Hom.: 175

Bravo AF: 0.186

Asia WGS AF: 0.116 AC: 406 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3136604; hg19: chr3-172226081;