ENST00000714430.1:c.-359+2240A>G

Variant names:

• chr1-173474392-T-C
• rs10753081
• ENST00000714430.1:c.-359+2240A>G

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-359+2240A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,078 control chromosomes in the GnomAD database, including 29,951 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 0.60 (29951 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 2 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]

PRDX6-AS1 (HGNC:54870): (PRDX6 antisense RNA 1)

LOC100506023 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.757 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.524+2240A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-359+2240A>G		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-342+2240A>G		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-309+2240A>G		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91884 AN: 151960 Hom.: 29963 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.604 AC: 91876 AN: 152078 Hom.: 29951 Cov.: 32 AF XY: 0.608 AC XY: 45228 AN XY: 74342

African (AFR) AF: 0.350 AC: 14513 AN: 41460

American (AMR) AF: 0.716 AC: 10942 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2226 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2091 AN: 5174

South Asian (SAS) AF: 0.778 AC: 3748 AN: 4818

European-Finnish (FIN) AF: 0.721 AC: 7610 AN: 10558

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48529 AN: 67994

Other (OTH) AF: 0.648 AC: 1368 AN: 2110

Alfa AF: 0.667 Hom.: 13361

Bravo AF: 0.589

Asia WGS AF: 0.558 AC: 1941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.2
DANN	Benign	0.93
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs10753081; hg19: chr1-173443531;