rs12739142

Variant names:

• chr1-173475516-A-G
• rs12739142
• ENST00000714430.1:c.-359+1116T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000714430.1(TNFSF4):​c.-359+1116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 152,370 control chromosomes in the GnomAD database, including 95 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 0.029 (95 hom., cov: 34)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 1 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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0286 (4363/152370) while in subpopulation NFE AF = 0.0452 (3078/68032). AF 95% confidence interval is 0.0439. There are 95 homozygotes in GnomAd4. There are 2007 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 95 Unknown gene

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+1116T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-359+1116T>C		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-342+1116T>C		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-309+1116T>C		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4367 AN: 152252 Hom.: 95 Cov.: 34

Gnomad AFR AF: 0.00731

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0358

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

GnomAD4 genome AF: 0.0286 AC: 4363 AN: 152370 Hom.: 95 Cov.: 34 AF XY: 0.0269 AC XY: 2007 AN XY: 74510

African (AFR) AF: 0.00726 AC: 302 AN: 41588

American (AMR) AF: 0.0271 AC: 415 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5192

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4830

European-Finnish (FIN) AF: 0.0210 AC: 223 AN: 10626

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0452 AC: 3078 AN: 68032

Other (OTH) AF: 0.0350 AC: 74 AN: 2116

Alfa AF: 0.0411 Hom.: 29

Bravo AF: 0.0280

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.45
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs12739142; hg19: chr1-173444655;