rs4894559

Positions:

• chr3-172515579-A-G
• chr3-172515579-A-T

Variant summary

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

The NM_003810.4(TNFSF10):​c.133-581T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,146 control chromosomes in the GnomAD database, including 46,263 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 0.77 (46263 hom., cov: 31)
• Consequence: TNFSF10 NM_003810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF10	NM_003810.4	c.133-581T>C		intron_variant		ENST00000241261.7	NP_003801.1
TNFSF10	NM_001190942.2	c.133-581T>C		intron_variant			NP_001177871.1
TNFSF10	NR_033994.2	n.179-581T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7	c.133-581T>C		intron_variant		1	NM_003810.4	ENSP00000241261	P1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117695 AN: 152028 Hom.: 46224 Cov.: 31

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.774 AC: 117786 AN: 152146 Hom.: 46263 Cov.: 31 AF XY: 0.768 AC XY: 57120 AN XY: 74370

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.828

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.792

Alfa AF: 0.752 Hom.: 57853

Bravo AF: 0.775

Asia WGS AF: 0.734 AC: 2549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.025
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs4894559; hg19: chr3-172233369;