rs1356188583

Variant names:

• chr17-7556907-GC-G
• rs1356188583
• NM_003809.3:c.498+9delC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_003809.3(TNFSF12):​c.498+9delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000073 in 1,369,788 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000073 (1 hom.)
• Consequence: TNFSF12 NM_003809.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.450
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 17-7556907-GC-G is Benign according to our data. Variant chr17-7556907-GC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 455756.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 10 AD gene.

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.498+9delC		intron	N/A	NP_003800.1
	TNFSF12-TNFSF13	NM_172089.4		c.498+9delC		intron	N/A	NP_742086.1
	TNFSF12	NR_037146.2		n.833+9delC		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF12	ENST00000293825.11	TSL:1 MANE Select	c.498+6delC		splice_region intron	N/A	ENSP00000293825.6
	TNFSF12-TNFSF13	ENST00000293826.4	TSL:1	c.498+6delC		splice_region intron	N/A	ENSP00000293826.4
	TNFSF12	ENST00000322272.11	TSL:1	n.*332+6delC		splice_region intron	N/A	ENSP00000314636.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 180952 AF XY: 0.0000105

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000893

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000730 AC: 10 AN: 1369788 Hom.: 1 Cov.: 31 AF XY: 0.00000745 AC XY: 5 AN XY: 670968

African (AFR) AF: 0.00 AC: 0 AN: 30554

American (AMR) AF: 0.000322 AC: 10 AN: 31028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20292

East Asian (EAS) AF: 0.00 AC: 0 AN: 38694

South Asian (SAS) AF: 0.00 AC: 0 AN: 72102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065634

Other (OTH) AF: 0.00 AC: 0 AN: 56286

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Common variable immunodeficiency Benign:1

Jul 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45

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: rs1356188583; hg19: chr17-7460224;