chr1-173473779-G-C

Variant names:

• chr1-173473779-G-C
• rs113102066
• ENST00000714430.1:c.-359+2853C>G

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+2853C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 152,124 control chromosomes in the GnomAD database, including 37 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 0.018 (37 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656
• Publications: 0 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 sas. GnomAd4 allele frequency = 0.0181 (2754/152124) while in subpopulation SAS AF = 0.0315 (152/4820). AF 95% confidence interval is 0.0274. There are 37 homozygotes in GnomAd4. There are 1438 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100506023	NR_037845.1		n.524+2853C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-359+2853C>G		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-342+2853C>G		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-309+2853C>G		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2756 AN: 152006 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.00358

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0181 AC: 2754 AN: 152124 Hom.: 37 Cov.: 32 AF XY: 0.0193 AC XY: 1438 AN XY: 74360

African (AFR) AF: 0.00357 AC: 148 AN: 41506

American (AMR) AF: 0.0113 AC: 173 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4820

European-Finnish (FIN) AF: 0.0560 AC: 592 AN: 10564

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0221 AC: 1505 AN: 67992

Other (OTH) AF: 0.0161 AC: 34 AN: 2108

Alfa AF: 0.00765 Hom.: 2

Bravo AF: 0.0140

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.34
PhyloP100		0.66

Splicing

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

Other links and lift over

dbSNP: rs113102066; hg19: chr1-173442918;