3-172515579-A-G

Variant names:

• chr3-172515579-A-G
• rs4894559
• NM_003810.4:c.133-581T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003810.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	NM_003810.4	MANE Select	c.133-581T>C		intron	N/A	NP_003801.1
	TNFSF10	NM_001190942.2		c.133-581T>C		intron	N/A	NP_001177871.1
	TNFSF10	NR_033994.2		n.179-581T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	ENST00000241261.7	TSL:1 MANE Select	c.133-581T>C		intron	N/A	ENSP00000241261.2
	TNFSF10	ENST00000420541.6	TSL:1	c.133-581T>C		intron	N/A	ENSP00000389931.2
	TNFSF10	ENST00000430881.1	TSL:5	n.58-581T>C		intron	N/A	ENSP00000404008.1

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

African (AFR) AF: 0.897 AC: 37259 AN: 41538

American (AMR) AF: 0.658 AC: 10059 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2872 AN: 3470

East Asian (EAS) AF: 0.721 AC: 3733 AN: 5178

South Asian (SAS) AF: 0.739 AC: 3562 AN: 4818

European-Finnish (FIN) AF: 0.681 AC: 7189 AN: 10556

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50387 AN: 67994

Other (OTH) AF: 0.792 AC: 1667 AN: 2106

Alfa AF: 0.759 Hom.: 93932

Bravo AF: 0.775

Asia WGS AF: 0.734 AC: 2549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.025
DANN	Benign	0.57
PhyloP100		-1.4
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: rs4894559; hg19: chr3-172233369;