1-173475908-A-G

Variant names:

• chr1-173475908-A-G
• rs34619706
• ENST00000714430.1:c.-359+724T>C

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-359+724T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 152,294 control chromosomes in the GnomAD database, including 756 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 0.082 (756 hom., cov: 33)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100506023	NR_037845.1		n.524+724T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-359+724T>C		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-342+724T>C		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-309+724T>C		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.0823 AC: 12528 AN: 152176 Hom.: 754 Cov.: 33

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0984

Gnomad OTH AF: 0.0742

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

GnomAD4 genome AF: 0.0823 AC: 12540 AN: 152294 Hom.: 756 Cov.: 33 AF XY: 0.0845 AC XY: 6293 AN XY: 74450

African (AFR) AF: 0.0228 AC: 948 AN: 41574

American (AMR) AF: 0.0628 AC: 960 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3472

East Asian (EAS) AF: 0.284 AC: 1468 AN: 5178

South Asian (SAS) AF: 0.104 AC: 504 AN: 4828

European-Finnish (FIN) AF: 0.144 AC: 1525 AN: 10600

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0984 AC: 6693 AN: 68026

Other (OTH) AF: 0.0772 AC: 163 AN: 2112

Alfa AF: 0.0780 Hom.: 256

Bravo AF: 0.0742

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.50
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs34619706; hg19: chr1-173445047;