1-173182017-G-T

Variant names:

• chr1-173182017-G-T
• rs10127728
• ENST00000714429.1:c.202+6504C>A

Variant summary

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

The ENST00000714429.1(TNFSF4):​c.202+6504C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,032 control chromosomes in the GnomAD database, including 6,874 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 0.25 (6874 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714429.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 14 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000714429.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714429.1		c.202+6504C>A		intron	N/A	ENSP00000519698.1	A0AAQ5BI34
	TNFSF4	ENST00000714452.1		n.409+6504C>A		intron	N/A
	TNFSF4	ENST00000714453.1		n.294+6504C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37173 AN: 151914 Hom.: 6845 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0765

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.245 AC: 37251 AN: 152032 Hom.: 6874 Cov.: 32 AF XY: 0.245 AC XY: 18201 AN XY: 74328

African (AFR) AF: 0.519 AC: 21491 AN: 41442

American (AMR) AF: 0.237 AC: 3616 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3468

East Asian (EAS) AF: 0.0765 AC: 396 AN: 5176

South Asian (SAS) AF: 0.122 AC: 588 AN: 4822

European-Finnish (FIN) AF: 0.144 AC: 1522 AN: 10560

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8516 AN: 67970

Other (OTH) AF: 0.226 AC: 477 AN: 2108

Alfa AF: 0.158 Hom.: 4405

Bravo AF: 0.264

Asia WGS AF: 0.159 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.35
PhyloP100		-0.25

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: rs10127728;

hg19: chr1-173151156;