rs3774315

Variant names:

• chr3-172514196-A-G
• rs3774315
• NM_003810.4:c.270+665T>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.270+665T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,194 control chromosomes in the GnomAD database, including 4,454 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 (4454 hom., cov: 32)
• Consequence: TNFSF10 NM_003810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 14 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 (NFE) allele frequency at 95% confidence interval = 0.274 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	NM_003810.4	MANE Select	c.270+665T>C		intron	N/A	NP_003801.1
	TNFSF10	NM_001190942.2		c.270+665T>C		intron	N/A	NP_001177871.1
	TNFSF10	NR_033994.2		n.316+665T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	ENST00000241261.7	TSL:1 MANE Select	c.270+665T>C		intron	N/A	ENSP00000241261.2
	TNFSF10	ENST00000420541.6	TSL:1	c.270+665T>C		intron	N/A	ENSP00000389931.2
	TNFSF10	ENST00000855872.1		c.270+665T>C		intron	N/A	ENSP00000525931.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34523 AN: 152078 Hom.: 4459 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.227 AC: 34522 AN: 152194 Hom.: 4454 Cov.: 32 AF XY: 0.229 AC XY: 17065 AN XY: 74408

African (AFR) AF: 0.120 AC: 4966 AN: 41530

American (AMR) AF: 0.223 AC: 3404 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1369 AN: 3468

East Asian (EAS) AF: 0.168 AC: 871 AN: 5184

South Asian (SAS) AF: 0.200 AC: 967 AN: 4824

European-Finnish (FIN) AF: 0.291 AC: 3077 AN: 10582

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18866 AN: 67998

Other (OTH) AF: 0.263 AC: 555 AN: 2108

Alfa AF: 0.265 Hom.: 21531

Bravo AF: 0.217

Asia WGS AF: 0.149 AC: 520 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	3.7
DANN	Benign	0.71
PhyloP100		0.19
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: rs3774315; hg19: chr3-172231986;