rs4916314

chr1-173203019-C-Achr1-173203019-C-T

Variant summary

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

The NM_003326.5(TNFSF4):c.153+4005G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,130 control chromosomes in the GnomAD database, including 2,136 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 0.15 (2136 hom., cov: 32)
• Consequence: TNFSF4 NM_003326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF4	NM_003326.5	c.153+4005G>T		intron_variant		ENST00000281834.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF4	ENST00000281834.4	c.153+4005G>T		intron_variant		1	NM_003326.5	P1
TNFSF4	ENST00000367718.5	c.3+2292G>T		intron_variant		1
TNFSF4	ENST00000488053.1	n.414+2292G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22688 AN: 152014 Hom.: 2132 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.149 AC: 22692 AN: 152130 Hom.: 2136 Cov.: 32 AF XY: 0.148 AC XY: 11015 AN XY: 74342

Gnomad4 AFR AF: 0.0509

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.0233

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.180

Alfa AF: 0.0803 Hom.: 111

Bravo AF: 0.144

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.7
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4916314; hg19: chr1-173172158;