chr1-173332377-G-A

Variant names:

• chr1-173332377-G-A
• rs1342038
• ENST00000714430.1:c.-127+91497C>T

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-127+91497C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 151,926 control chromosomes in the GnomAD database, including 14,390 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 0.43 (14390 hom., cov: 31)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• Publications: 16 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]

TNFSF4 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• myocardial infarction, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

LOC100506023 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 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.656-92354C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-127+91497C>T		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-210-615C>T		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-9-125192C>T		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65580 AN: 151808 Hom.: 14387 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.432 AC: 65621 AN: 151926 Hom.: 14390 Cov.: 31 AF XY: 0.435 AC XY: 32329 AN XY: 74264

African (AFR) AF: 0.454 AC: 18811 AN: 41400

American (AMR) AF: 0.478 AC: 7296 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1705 AN: 3472

East Asian (EAS) AF: 0.599 AC: 3095 AN: 5164

South Asian (SAS) AF: 0.495 AC: 2385 AN: 4816

European-Finnish (FIN) AF: 0.407 AC: 4298 AN: 10550

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26578 AN: 67960

Other (OTH) AF: 0.427 AC: 902 AN: 2110

Alfa AF: 0.413 Hom.: 53689

Bravo AF: 0.441

Asia WGS AF: 0.510 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.30
PhyloP100		-0.15

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: rs1342038;

hg19: chr1-173301516;