ENST00000714430.1:c.-126-40832G>A

Variant names:

• chr1-173280855-C-T
• rs12405577
• ENST00000714430.1:c.-126-40832G>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-40832G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,074 control chromosomes in the GnomAD database, including 3,495 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 (3495 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 6 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

LOC100506023 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100506023	NR_037845.1	n.656-40832G>A		intron_variant	Intron 2 of 2
TNFSF4	XM_047429896.1	c.148-73670G>A		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-73670G>A		intron_variant	Intron 2 of 4		XP_047285858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF4	ENST00000714430.1	c.-126-40832G>A		intron_variant	Intron 3 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-126-40832G>A		intron_variant	Intron 3 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-73670G>A		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29284 AN: 151956 Hom.: 3490 Cov.: 32

Gnomad AFR AF: 0.0501

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.193 AC: 29300 AN: 152074 Hom.: 3495 Cov.: 32 AF XY: 0.194 AC XY: 14457 AN XY: 74330

African (AFR) AF: 0.0500 AC: 2076 AN: 41528

American (AMR) AF: 0.313 AC: 4771 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1247 AN: 5158

South Asian (SAS) AF: 0.199 AC: 961 AN: 4818

European-Finnish (FIN) AF: 0.245 AC: 2590 AN: 10550

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

European-Non Finnish (NFE) AF: 0.239 AC: 16245 AN: 67976

Other (OTH) AF: 0.205 AC: 433 AN: 2114

Alfa AF: 0.204 Hom.: 453

Bravo AF: 0.196

Asia WGS AF: 0.210 AC: 729 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.42
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs12405577; hg19: chr1-173249994;