17-7557242-G-T

Variant names:

• chr17-7557242-G-T
• rs4968189
• NM_003809.3:c.642G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_003809.3(TNFSF12):​c.642G>T​(p.Gly214Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,613,724 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (70 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (62 hom.)
• Consequence: TNFSF12 NM_003809.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13
• Publications: 10 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 17-7557242-G-T is Benign according to our data. Variant chr17-7557242-G-T is described in ClinVar as Benign. ClinVar VariationId is 455758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0541 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.642G>T	p.Gly214Gly	synonymous	Exon 7 of 7	NP_003800.1
	TNFSF12	NR_037146.2		n.977G>T		non_coding_transcript_exon	Exon 8 of 8
	TNFSF12-TNFSF13	NM_172089.4		c.498+340G>T		intron	N/A	NP_742086.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF12	ENST00000293825.11	TSL:1 MANE Select	c.642G>T	p.Gly214Gly	synonymous	Exon 7 of 7	ENSP00000293825.6
	TNFSF12	ENST00000322272.11	TSL:1	n.*476G>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000314636.7
	TNFSF12	ENST00000322272.11	TSL:1	n.*476G>T		3_prime_UTR	Exon 8 of 8	ENSP00000314636.7

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2443 AN: 152124 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00957

GnomAD4 exome AF: 0.00171 AC: 2492 AN: 1461482 Hom.: 62 Cov.: 68 AF XY: 0.00147 AC XY: 1072 AN XY: 727062

African (AFR) AF: 0.0591 AC: 1979 AN: 33478

American (AMR) AF: 0.00313 AC: 140 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.0000737 AC: 82 AN: 1111972

Other (OTH) AF: 0.00422 AC: 255 AN: 60386

GnomAD4 genome AF: 0.0161 AC: 2452 AN: 152242 Hom.: 70 Cov.: 32 AF XY: 0.0154 AC XY: 1144 AN XY: 74444

African (AFR) AF: 0.0560 AC: 2325 AN: 41532

American (AMR) AF: 0.00588 AC: 90 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67996

Other (OTH) AF: 0.00947 AC: 20 AN: 2112

Alfa AF: 0.00751 Hom.: 30

Bravo AF: 0.0187

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Common variable immunodeficiency Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.1
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4968189; hg19: chr17-7460559;