ENST00000714430.1:c.-10+1210C>T

Variant names:

• chr1-173238697-G-A
• rs844642
• ENST00000714430.1:c.-10+1210C>T

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-10+1210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 150,576 control chromosomes in the GnomAD database, including 33,772 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 0.64 (33772 hom., cov: 31)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• 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]

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 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.1982C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-10+1210C>T		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-10+1210C>T		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-9-31512C>T		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 96839 AN: 150458 Hom.: 33705 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.644 AC: 96966 AN: 150576 Hom.: 33772 Cov.: 31 AF XY: 0.643 AC XY: 47306 AN XY: 73514

African (AFR) AF: 0.916 AC: 37986 AN: 41476

American (AMR) AF: 0.661 AC: 10060 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1788 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2257 AN: 5144

South Asian (SAS) AF: 0.540 AC: 2594 AN: 4800

European-Finnish (FIN) AF: 0.518 AC: 5280 AN: 10198

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.524 AC: 35061 AN: 66970

Other (OTH) AF: 0.640 AC: 1341 AN: 2096

Alfa AF: 0.580 Hom.: 3451

Bravo AF: 0.663

Asia WGS AF: 0.529 AC: 1839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.81
DANN	Benign	0.35
PhyloP100		-0.83

Splicing

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

Other links and lift over

dbSNP: rs844642; hg19: chr1-173207836;