rs844648

Variant names:

• chr1-173254724-G-A
• rs844648
• ENST00000714430.1:c.-126-14701C>T

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-14701C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,010 control chromosomes in the GnomAD database, including 16,208 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 0.46 (16208 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 38 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
• myocardial infarction, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

LOC100506023 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.515 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100506023	NR_037845.1		n.656-14701C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-14701C>T		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-126-14701C>T		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-9-47539C>T		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69485 AN: 151892 Hom.: 16179 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.458 AC: 69554 AN: 152010 Hom.: 16208 Cov.: 32 AF XY: 0.458 AC XY: 34052 AN XY: 74302

African (AFR) AF: 0.518 AC: 21469 AN: 41452

American (AMR) AF: 0.525 AC: 8021 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3466

East Asian (EAS) AF: 0.443 AC: 2290 AN: 5172

South Asian (SAS) AF: 0.410 AC: 1973 AN: 4818

European-Finnish (FIN) AF: 0.410 AC: 4322 AN: 10540

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28705 AN: 67956

Other (OTH) AF: 0.458 AC: 969 AN: 2114

Alfa AF: 0.435 Hom.: 44769

Bravo AF: 0.471

Asia WGS AF: 0.440 AC: 1530 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs844648; hg19: chr1-173223863;