Variant 17-7549225-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003809.3(TNFSF12):c.72C>T(p.Leu24=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,359,524 control chromosomes in the GnomAD database, including 7,921 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1192 hom., cov: 32)

Exomes 𝑓: 0.10 ( 6729 hom. )

Consequence

TNFSF12
NM_003809.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.71

Variant links:

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 links:

TNFSF12-TNFSF13 (HGNC:):

TNFSF12-TNFSF13 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 17-7549225-C-T is Benign according to our data. Variant chr17-7549225-C-T is described in ClinVar as [Benign]. Clinvar id is 1168780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNFSF12	NM_003809.3 linkuse as main transcript	c.72C>T	p.Leu24=	synonymous_variant	1/7	ENST00000293825.11	NP_003800.1
TNFSF12-TNFSF13	NM_172089.4 linkuse as main transcript	c.72C>T	p.Leu24=	synonymous_variant	1/11		NP_742086.1
TNFSF12	NR_037146.2 linkuse as main transcript	n.168C>T		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF12	ENST00000293825.11 linkuse as main transcript	c.72C>T	p.Leu24=	synonymous_variant	1/7	1	NM_003809.3	ENSP00000293825	P4	O43508-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17258

AN:

152014

Hom.:

1178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.0758

Gnomad AMR

AF:

0.0823

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.0482

Gnomad FIN

AF:

0.0340

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0965

Gnomad OTH

AF:

0.0974

GnomAD3 exomes

AF:

0.0728

AC:

1285

AN:

17648

Hom.:

AF XY:

0.0681

AC XY:

732

AN XY:

10742

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.0554

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.110

Gnomad SAS exome

AF:

0.0321

Gnomad FIN exome

AF:

0.0334

Gnomad NFE exome

AF:

0.0938

Gnomad OTH exome

AF:

0.0806

GnomAD4 exome

AF:

0.101

AC:

122301

AN:

1207396

Hom.:

6729

Cov.:

AF XY:

0.0986

AC XY:

57864

AN XY:

586814

show subpopulations

Gnomad4 AFR exome

AF:

0.181

Gnomad4 AMR exome

AF:

0.0689

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.0390

Gnomad4 FIN exome

AF:

0.0416

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.114

AC:

17302

AN:

152128

Hom.:

1192

Cov.:

AF XY:

0.108

AC XY:

8051

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.184

Gnomad4 AMR

AF:

0.0821

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.0485

Gnomad4 FIN

AF:

0.0340

Gnomad4 NFE

AF:

0.0965

Gnomad4 OTH

AF:

0.0964

Alfa

AF:

0.0967

Hom.:

186

Bravo

AF:

0.126

Asia WGS

AF:

0.0790

AC:

273

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 2018	- -

Common variable immunodeficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.2

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over