chr1-173285369-T-C

Variant names:

• chr1-173285369-T-C
• rs12143114
• ENST00000714430.1:c.-126-45346A>G

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-45346A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,022 control chromosomes in the GnomAD database, including 7,695 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 0.31 (7695 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.391 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.656-45346A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-45346A>G		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-126-45346A>G		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-9-78184A>G		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46616 AN: 151904 Hom.: 7687 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.307 AC: 46651 AN: 152022 Hom.: 7695 Cov.: 32 AF XY: 0.310 AC XY: 23007 AN XY: 74290

African (AFR) AF: 0.190 AC: 7900 AN: 41502

American (AMR) AF: 0.400 AC: 6106 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 986 AN: 3466

East Asian (EAS) AF: 0.267 AC: 1377 AN: 5158

South Asian (SAS) AF: 0.311 AC: 1496 AN: 4818

European-Finnish (FIN) AF: 0.370 AC: 3905 AN: 10540

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23808 AN: 67952

Other (OTH) AF: 0.315 AC: 665 AN: 2112

Alfa AF: 0.336 Hom.: 3052

Bravo AF: 0.307

Asia WGS AF: 0.289 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.76
PhyloP100		0.20

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: rs12143114;

hg19: chr1-173254508;