chr17-7549660-C-T

Position:

• chr17-7549660-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.207+139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,308,790 control chromosomes in the GnomAD database, including 373,403 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 0.76 (44505 hom., cov: 31)
  • Exomes 𝑓: 0.75 (328898 hom.)
• Consequence: TNFSF12 NM_003809.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF12	NM_003809.3	c.207+139C>T		intron_variant		ENST00000293825.11	NP_003800.1
TNFSF12-TNFSF13	NM_172089.4	c.207+139C>T		intron_variant			NP_742086.1
TNFSF12	NR_037146.2	n.303+139C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF12	ENST00000293825.11	c.207+139C>T		intron_variant		1	NM_003809.3	ENSP00000293825.6
TNFSF12-TNFSF13	ENST00000293826.4	c.207+139C>T		intron_variant		1		ENSP00000293826.4

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115772 AN: 151880 Hom.: 44465 Cov.: 31

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.763

GnomAD4 exome AF: 0.751 AC: 868911 AN: 1156792 Hom.: 328898 Cov.: 17 AF XY: 0.754 AC XY: 422832 AN XY: 560990

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.855

Gnomad4 ASJ exome AF: 0.816

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.890

Gnomad4 FIN exome AF: 0.765

Gnomad4 NFE exome AF: 0.730

Gnomad4 OTH exome AF: 0.769

GnomAD4 genome AF: 0.762 AC: 115864 AN: 151998 Hom.: 44505 Cov.: 31 AF XY: 0.770 AC XY: 57261 AN XY: 74334

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.899

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.766

Alfa AF: 0.744 Hom.: 10449

Bravo AF: 0.765

Asia WGS AF: 0.935 AC: 3251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs9899183; hg19: chr17-7452977; COSMIC: COSV53433851; COSMIC: COSV53433851;