rs4382766

Variant names:

• chr1-173475937-C-T
• rs4382766
• ENST00000714430.1:c.-359+695G>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-359+695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,174 control chromosomes in the GnomAD database, including 30,067 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 0.61 (30067 hom., cov: 33)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100506023	NR_037845.1	n.524+695G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF4	ENST00000714430.1	c.-359+695G>A		intron_variant	Intron 1 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-342+695G>A		intron_variant	Intron 1 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-309+695G>A		intron_variant	Intron 1 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92259 AN: 152056 Hom.: 30080 Cov.: 33

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.606 AC: 92250 AN: 152174 Hom.: 30067 Cov.: 33 AF XY: 0.610 AC XY: 45406 AN XY: 74378

African (AFR) AF: 0.360 AC: 14934 AN: 41500

American (AMR) AF: 0.716 AC: 10942 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2225 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2081 AN: 5178

South Asian (SAS) AF: 0.776 AC: 3742 AN: 4820

European-Finnish (FIN) AF: 0.720 AC: 7625 AN: 10592

Middle Eastern (MID) AF: 0.678 AC: 198 AN: 292

European-Non Finnish (NFE) AF: 0.713 AC: 48477 AN: 68006

Other (OTH) AF: 0.650 AC: 1376 AN: 2116

Alfa AF: 0.628 Hom.: 4763

Bravo AF: 0.591

Asia WGS AF: 0.558 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.65
PhyloP100		2.2

Splicing

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

Other links and lift over

dbSNP: rs4382766; hg19: chr1-173445076;