1-173243134-C-T

Variant names:

• chr1-173243134-C-T
• rs12039904
• ENST00000714430.1:c.-126-3111G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000714430.1(TNFSF4):​c.-126-3111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,780 control chromosomes in the GnomAD database, including 3,469 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 0.19 (3469 hom., cov: 30)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 24 publications found

Genes affected

TNFSF4 (HGNC:11934): (TNF superfamily member 4) This gene encodes a cytokine of the tumor necrosis factor (TNF) ligand family. The encoded protein functions in T cell antigen-presenting cell (APC) interactions and mediates adhesion of activated T cells to endothelial cells. Polymorphisms in this gene have been associated with Sjogren's syndrome and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

TNFSF4 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• myocardial infarction, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

LOC100506023 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000714430.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100506023	NR_037845.1		n.656-3111G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-3111G>A		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-126-3111G>A		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-9-35949G>A		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29161 AN: 151662 Hom.: 3465 Cov.: 30

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.192 AC: 29178 AN: 151780 Hom.: 3469 Cov.: 30 AF XY: 0.194 AC XY: 14411 AN XY: 74152

African (AFR) AF: 0.0477 AC: 1976 AN: 41432

American (AMR) AF: 0.315 AC: 4794 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 650 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1257 AN: 5162

South Asian (SAS) AF: 0.204 AC: 980 AN: 4804

European-Finnish (FIN) AF: 0.236 AC: 2483 AN: 10500

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16284 AN: 67908

Other (OTH) AF: 0.200 AC: 420 AN: 2100

Alfa AF: 0.204 Hom.: 453

Bravo AF: 0.195

Asia WGS AF: 0.210 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.41
PhyloP100		0.21

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12039904;

hg19: chr1-173212273;