1-173476539-G-T

Variant names:

• chr1-173476539-G-T
• rs11576174
• ENST00000714430.1:c.-359+93C>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+93C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,202 control chromosomes in the GnomAD database, including 1,150 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 0.11 (1150 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.162 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+93C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-359+93C>A		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-342+93C>A		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-309+93C>A		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16194 AN: 152084 Hom.: 1150 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.106 AC: 16192 AN: 152202 Hom.: 1150 Cov.: 32 AF XY: 0.105 AC XY: 7822 AN XY: 74386

African (AFR) AF: 0.0268 AC: 1114 AN: 41556

American (AMR) AF: 0.102 AC: 1558 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3472

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5180

South Asian (SAS) AF: 0.172 AC: 829 AN: 4822

European-Finnish (FIN) AF: 0.125 AC: 1317 AN: 10564

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10509 AN: 68008

Other (OTH) AF: 0.119 AC: 251 AN: 2112

Alfa AF: 0.144 Hom.: 3603

Bravo AF: 0.100

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.59
PhyloP100		0.065

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11576174;

hg19: chr1-173445678;