chr1-173472494-G-A

Variant names:

• chr1-173472494-G-A
• rs4916362
• ENST00000714430.1:c.-359+4138C>T

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-359+4138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,014 control chromosomes in the GnomAD database, including 29,695 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 0.60 (29695 hom., cov: 31)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.756 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.524+4138C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-359+4138C>T		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-342+4138C>T		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-309+4138C>T		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91153 AN: 151898 Hom.: 29707 Cov.: 31

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.689

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.600 AC: 91146 AN: 152014 Hom.: 29695 Cov.: 31 AF XY: 0.604 AC XY: 44883 AN XY: 74304

African (AFR) AF: 0.335 AC: 13895 AN: 41424

American (AMR) AF: 0.714 AC: 10913 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2223 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2089 AN: 5170

South Asian (SAS) AF: 0.777 AC: 3747 AN: 4824

European-Finnish (FIN) AF: 0.721 AC: 7629 AN: 10582

Middle Eastern (MID) AF: 0.676 AC: 196 AN: 290

European-Non Finnish (NFE) AF: 0.713 AC: 48446 AN: 67956

Other (OTH) AF: 0.645 AC: 1357 AN: 2104

Alfa AF: 0.679 Hom.: 16465

Bravo AF: 0.584

Asia WGS AF: 0.557 AC: 1938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.72
DANN	Benign	0.44
PhyloP100		-0.52

Splicing

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

Other links and lift over

dbSNP: rs4916362; hg19: chr1-173441633;