ENST00000714430.1:c.-126-40610G>A

Variant names:

• chr1-173280633-C-T
• rs12750070
• ENST00000714430.1:c.-126-40610G>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-40610G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,924 control chromosomes in the GnomAD database, including 7,323 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 0.30 (7323 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• 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

LOC100506023 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.388 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100506023	NR_037845.1		n.656-40610G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-40610G>A		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-126-40610G>A		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-9-73448G>A		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45208 AN: 151806 Hom.: 7317 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.298 AC: 45241 AN: 151924 Hom.: 7323 Cov.: 32 AF XY: 0.300 AC XY: 22273 AN XY: 74220

African (AFR) AF: 0.172 AC: 7144 AN: 41442

American (AMR) AF: 0.397 AC: 6046 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3466

East Asian (EAS) AF: 0.267 AC: 1376 AN: 5156

South Asian (SAS) AF: 0.310 AC: 1489 AN: 4810

European-Finnish (FIN) AF: 0.349 AC: 3673 AN: 10532

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.346 AC: 23483 AN: 67962

Other (OTH) AF: 0.310 AC: 656 AN: 2116

Alfa AF: 0.324 Hom.: 4790

Bravo AF: 0.300

Asia WGS AF: 0.287 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.26
DANN	Benign	0.71
PhyloP100		-0.37

Splicing

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

Other links and lift over

dbSNP: rs12750070; hg19: chr1-173249772;