3-172518650-T-G

Position:

• chr3-172518650-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003810.4(TNFSF10):​c.133-3652A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,036 control chromosomes in the GnomAD database, including 18,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.48 (18585 hom., cov: 32)
• Consequence: TNFSF10 NM_003810.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.29

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-172518650-T-G is Benign according to our data. Variant chr3-172518650-T-G is described in ClinVar as [Benign]. Clinvar id is 1287431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF10	NM_003810.4	c.133-3652A>C		intron_variant		ENST00000241261.7	NP_003801.1
TNFSF10	NM_001190942.2	c.133-3652A>C		intron_variant			NP_001177871.1
TNFSF10	NM_001190943.2	c.133-185A>C		intron_variant			NP_001177872.1
TNFSF10	NR_033994.2	n.179-3652A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7	c.133-3652A>C		intron_variant		1	NM_003810.4	ENSP00000241261	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72803 AN: 151918 Hom.: 18567 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.479 AC: 72870 AN: 152036 Hom.: 18585 Cov.: 32 AF XY: 0.486 AC XY: 36092 AN XY: 74310

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.442

Alfa AF: 0.405 Hom.: 30124

Bravo AF: 0.488

Asia WGS AF: 0.740 AC: 2570 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.6
DANN	Benign	0.73

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: rs231983; hg19: chr3-172236440;