NM_003809.3:c.207+139C>T

Variant names:

• chr17-7549660-C-T
• rs9899183
• NM_003809.3:c.207+139C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003809.3. 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.207+139C>T		intron	N/A	NP_003800.1
	TNFSF12-TNFSF13	NM_172089.4		c.207+139C>T		intron	N/A	NP_742086.1
	TNFSF12	NR_037146.2		n.303+139C>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.207+139C>T		intron	N/A	ENSP00000293825.6
	TNFSF12-TNFSF13	ENST00000293826.4	TSL:1	c.207+139C>T		intron	N/A	ENSP00000293826.4
	TNFSF12	ENST00000322272.11	TSL:1	n.207+139C>T		intron	N/A	ENSP00000314636.7

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

African (AFR) AF: 0.731 AC: 19228 AN: 26316

American (AMR) AF: 0.855 AC: 16544 AN: 19358

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 14120 AN: 17296

East Asian (EAS) AF: 0.999 AC: 33242 AN: 33260

South Asian (SAS) AF: 0.890 AC: 46181 AN: 51868

European-Finnish (FIN) AF: 0.765 AC: 22345 AN: 29218

Middle Eastern (MID) AF: 0.767 AC: 3564 AN: 4644

European-Non Finnish (NFE) AF: 0.730 AC: 676413 AN: 926344

Other (OTH) AF: 0.769 AC: 37274 AN: 48488

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

African (AFR) AF: 0.734 AC: 30373 AN: 41386

American (AMR) AF: 0.823 AC: 12576 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2849 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5150 AN: 5162

South Asian (SAS) AF: 0.899 AC: 4339 AN: 4828

European-Finnish (FIN) AF: 0.777 AC: 8216 AN: 10580

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.734 AC: 49915 AN: 67984

Other (OTH) AF: 0.766 AC: 1617 AN: 2112

Alfa AF: 0.743 Hom.: 16426

Bravo AF: 0.765

Asia WGS AF: 0.935 AC: 3251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.78
PhyloP100		-0.052
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9899183; hg19: chr17-7452977; COSMIC: COSV53433851; COSMIC: COSV53433851;