chr1-173475697-C-G

Variant names:

• chr1-173475697-C-G
• rs4354572
• ENST00000714430.1:c.-359+935G>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+935G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00979 in 152,330 control chromosomes in the GnomAD database, including 25 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 0.0098 (25 hom., cov: 33)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• 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=-0.88).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00979 (1492/152330) while in subpopulation AFR AF = 0.0345 (1433/41538). AF 95% confidence interval is 0.033. There are 25 homozygotes in GnomAd4. There are 704 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 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+935G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-359+935G>C		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-342+935G>C		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-309+935G>C		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.00977 AC: 1487 AN: 152212 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00669

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

GnomAD4 genome AF: 0.00979 AC: 1492 AN: 152330 Hom.: 25 Cov.: 33 AF XY: 0.00945 AC XY: 704 AN XY: 74496

African (AFR) AF: 0.0345 AC: 1433 AN: 41538

American (AMR) AF: 0.00255 AC: 39 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68046

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00 Hom.: 4077

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		0.018

Splicing

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

Other links and lift over

dbSNP: rs4354572; hg19: chr1-173444836;