chr17-7552219-C-T

Position:

• chr17-7552219-C-T

Variant summary

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

The NM_003809.3(TNFSF12):​c.373+1241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,954 control chromosomes in the GnomAD database, including 27,446 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 0.59 (27446 hom., cov: 33)
• Consequence: TNFSF12 NM_003809.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

Genes affected

TNFSF12 (HGNC:11927): (TNF superfamily member 12) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. This cytokine, which exists in both membrane-bound and secreted forms, can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis. Alternative splicing results in multiple transcript variants. Some transcripts skip the last exon of this gene and continue into the second exon of the neighboring TNFSF13 gene; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]

TNFSF12-TNFSF13 (HGNC:33537): (TNFSF12-TNFSF13 readthrough) This gene encodes a member of the tumor necrosis factor superfamily. It encodes a hybrid protein composed of the cytoplasmic and transmembrane domains of family member 12 fused to the C-terminal domain of family member 13. The hybrid protein is membrane anchored and presents the receptor-binding domain of family member 13 at the cell surface. It stimulates cycling in T- and B-lymphoma cell lines. [provided by RefSeq, Jul 2008]

TNFSF12 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF12	NM_003809.3	c.373+1241C>T		intron_variant		ENST00000293825.11	NP_003800.1
TNFSF12-TNFSF13	NM_172089.4	c.373+1241C>T		intron_variant			NP_742086.1
TNFSF12	NR_037146.2	n.469+1241C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF12	ENST00000293825.11	c.373+1241C>T		intron_variant		1	NM_003809.3	ENSP00000293825.6
TNFSF12-TNFSF13	ENST00000293826.4	c.373+1241C>T		intron_variant		1		ENSP00000293826.4

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90024 AN: 151836 Hom.: 27421 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.593 AC: 90094 AN: 151954 Hom.: 27446 Cov.: 33 AF XY: 0.596 AC XY: 44277 AN XY: 74262

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.602

Alfa AF: 0.648 Hom.: 51073

Bravo AF: 0.582

Asia WGS AF: 0.637 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.86

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: rs4511593; hg19: chr17-7455536; COSMIC: COSV53433869;