17-7552219-C-T

Variant names:

• chr17-7552219-C-T
• rs4511593
• NM_003809.3:c.373+1241C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172089.4(TNFSF12-TNFSF13):​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-TNFSF13 NM_172089.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 27 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172089.4. 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
	TNFSF12	NM_003809.3	MANE Select	c.373+1241C>T		intron	N/A	NP_003800.1
	TNFSF12-TNFSF13	NM_172089.4		c.373+1241C>T		intron	N/A	NP_742086.1
	TNFSF12	NR_037146.2		n.469+1241C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF12	ENST00000293825.11	TSL:1 MANE Select	c.373+1241C>T		intron	N/A	ENSP00000293825.6
	TNFSF12-TNFSF13	ENST00000293826.4	TSL:1	c.373+1241C>T		intron	N/A	ENSP00000293826.4
	TNFSF12	ENST00000322272.11	TSL:1	n.373+1241C>T		intron	N/A	ENSP00000314636.7

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

African (AFR) AF: 0.454 AC: 18770 AN: 41382

American (AMR) AF: 0.564 AC: 8615 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2552 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3454 AN: 5168

South Asian (SAS) AF: 0.696 AC: 3357 AN: 4826

European-Finnish (FIN) AF: 0.653 AC: 6889 AN: 10542

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44435 AN: 67972

Other (OTH) AF: 0.602 AC: 1271 AN: 2112

Alfa AF: 0.637 Hom.: 116570

Bravo AF: 0.582

Asia WGS AF: 0.637 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.86
PhyloP100		0.071
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: rs4511593; hg19: chr17-7455536; COSMIC: COSV53433869;