3-172506285-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003810.4(TNFSF10):c.*207G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 516,014 control chromosomes in the GnomAD database, including 55,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19701 hom., cov: 32)
  • Exomes 𝑓: 0.44 (35363 hom.)
• Consequence: TNFSF10 NM_003810.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.252

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-172506285-C-T is Benign according to our data. Variant chr3-172506285-C-T is described in ClinVar as [Benign]. Clinvar id is 1237910.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF10	NM_003810.4	c.*207G>A		3_prime_UTR_variant	5/5	ENST00000241261.7
TNFSF10	NM_001190942.2	c.*599G>A		3_prime_UTR_variant	3/3
TNFSF10	NR_033994.2	n.1056G>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF10	ENST00000241261.7	c.*207G>A		3_prime_UTR_variant	5/5	1	NM_003810.4	P1
TNFSF10	ENST00000420541.6	c.*599G>A		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75488 AN: 151908 Hom.: 19684 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.435 AC: 158380 AN: 363988 Hom.: 35363 Cov.: 5 AF XY: 0.432 AC XY: 81116 AN XY: 187624

Gnomad4 AFR exome AF: 0.658

Gnomad4 AMR exome AF: 0.364

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.412

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.431

Gnomad4 OTH exome AF: 0.450

GnomAD4 genome AF: 0.497 AC: 75548 AN: 152026 Hom.: 19701 Cov.: 32 AF XY: 0.493 AC XY: 36619 AN XY: 74316

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.476

Alfa AF: 0.427 Hom.: 13479

Bravo AF: 0.500

Asia WGS AF: 0.531 AC: 1843 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.1
Dann	Benign	0.26

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: rs1131535; hg19: chr3-172224075; COSMIC: COSV53844650; COSMIC: COSV53844650;