rs2105325

Variant names:

• chr1-173380586-A-C
• rs2105325
• ENST00000714430.1:c.-127+43288T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-173380586-A-C
• chr1-173380586-A-G
• chr1-173380586-A-T

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-127+43288T>G variant causes a intron change. The variant allele was found at a frequency of 0.8 in 151,980 control chromosomes in the GnomAD database, including 48,813 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 0.80 (48813 hom., cov: 30)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 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.655+81738T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-127+43288T>G		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-210-48824T>G		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-10+80607T>G		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121408 AN: 151862 Hom.: 48762 Cov.: 30

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.800 AC: 121520 AN: 151980 Hom.: 48813 Cov.: 30 AF XY: 0.802 AC XY: 59592 AN XY: 74292

African (AFR) AF: 0.874 AC: 36236 AN: 41450

American (AMR) AF: 0.798 AC: 12184 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2448 AN: 3470

East Asian (EAS) AF: 0.914 AC: 4717 AN: 5162

South Asian (SAS) AF: 0.820 AC: 3944 AN: 4808

European-Finnish (FIN) AF: 0.815 AC: 8623 AN: 10574

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50809 AN: 67946

Other (OTH) AF: 0.790 AC: 1662 AN: 2104

Alfa AF: 0.896 Hom.: 9052

Bravo AF: 0.802

Asia WGS AF: 0.852 AC: 2963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.91
DANN	Benign	0.37

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: rs2105325;

hg19: chr1-173349725;