chr1-173404044-T-C

Variant names:

• chr1-173404044-T-C
• rs4916219
• XM_047429902.1:c.-1590A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047429902.1(TNFSF4):​c.-1590A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,116 control chromosomes in the GnomAD database, including 35,177 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 0.68 (35177 hom., cov: 32)
• Consequence: TNFSF4 XM_047429902.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

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]

LOC100506023 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF4	XM_047429902.1	c.-1590A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5		XP_047285858.1
TNFSF4	XM_047429902.1	c.-1590A>G		5_prime_UTR_variant	Exon 1 of 5		XP_047285858.1
TNFSF4	XM_047429896.1	c.147+37875A>G		intron_variant	Intron 2 of 4		XP_047285852.1
LOC100506023	NR_037845.1	n.655+58280A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103399 AN: 151998 Hom.: 35161 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.680 AC: 103453 AN: 152116 Hom.: 35177 Cov.: 32 AF XY: 0.682 AC XY: 50720 AN XY: 74354

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.677

Alfa AF: 0.657 Hom.: 65994

Bravo AF: 0.681

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4916219; hg19: chr1-173373183;