chr1-173301510-A-C

Variant names:

• chr1-173301510-A-C
• rs1342032
• ENST00000714430.1:c.-126-61487T>G

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-61487T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,662 control chromosomes in the GnomAD database, including 24,595 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 0.57 (24595 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.623 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.656-61487T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-61487T>G		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-127+30169T>G		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-9-94325T>G		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85642 AN: 151542 Hom.: 24577 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.565 AC: 85695 AN: 151662 Hom.: 24595 Cov.: 32 AF XY: 0.563 AC XY: 41749 AN XY: 74142

African (AFR) AF: 0.460 AC: 19053 AN: 41386

American (AMR) AF: 0.571 AC: 8687 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2172 AN: 3456

East Asian (EAS) AF: 0.641 AC: 3286 AN: 5126

South Asian (SAS) AF: 0.640 AC: 3084 AN: 4822

European-Finnish (FIN) AF: 0.565 AC: 5955 AN: 10548

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41451 AN: 67792

Other (OTH) AF: 0.583 AC: 1230 AN: 2110

Alfa AF: 0.600 Hom.: 113980

Bravo AF: 0.560

Asia WGS AF: 0.627 AC: 2182 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	0.15
DANN	Benign	0.50
PhyloP100		-0.25

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: rs1342032;

hg19: chr1-173270649;