ENST00000714430.1:c.-9-15151C>A

Variant names:

• chr1-173222336-G-T
• rs2205960
• ENST00000714430.1:c.-9-15151C>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-9-15151C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,056 control chromosomes in the GnomAD database, including 3,092 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 0.18 (3092 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 118 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.29 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-9-15151C>A		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-9-15151C>A		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-9-15151C>A		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27880 AN: 151938 Hom.: 3087 Cov.: 32

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.183 AC: 27896 AN: 152056 Hom.: 3092 Cov.: 32 AF XY: 0.187 AC XY: 13860 AN XY: 74314

African (AFR) AF: 0.0544 AC: 2257 AN: 41482

American (AMR) AF: 0.297 AC: 4535 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3472

East Asian (EAS) AF: 0.241 AC: 1245 AN: 5170

South Asian (SAS) AF: 0.220 AC: 1056 AN: 4804

European-Finnish (FIN) AF: 0.221 AC: 2329 AN: 10558

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15142 AN: 67966

Other (OTH) AF: 0.192 AC: 405 AN: 2114

Alfa AF: 0.208 Hom.: 11814

Bravo AF: 0.186

Asia WGS AF: 0.220 AC: 764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.53
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs2205960; hg19: chr1-173191475;