rs10127728

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-173182017-G-A
• chr1-173182017-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000714429.1(TNFSF4):​c.202+6504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 152,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00012 (0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High AC in GnomAd4 at 18 Unknown,AD gene.

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>T		intron	N/A	ENSP00000519698.1	A0AAQ5BI34
	TNFSF4	ENST00000714452.1		n.409+6504C>T		intron	N/A
	TNFSF4	ENST00000714453.1		n.294+6504C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 151964 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000958

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

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74342

African (AFR) AF: 0.000121 AC: 5 AN: 41470

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67978

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00 Hom.: 4405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.93
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;