1-173256005-T-G

Variant names:

• chr1-173256005-T-G
• rs844651
• ENST00000714430.1:c.-126-15982A>C

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-15982A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,036 control chromosomes in the GnomAD database, including 11,023 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 0.38 (11023 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• Publications: 4 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

LOC100506023 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100506023	NR_037845.1	n.656-15982A>C		intron_variant	Intron 2 of 2
TNFSF4	XM_047429896.1	c.148-48820A>C		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-48820A>C		intron_variant	Intron 2 of 4		XP_047285858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF4	ENST00000714430.1	c.-126-15982A>C		intron_variant	Intron 3 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-126-15982A>C		intron_variant	Intron 3 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-48820A>C		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57323 AN: 151918 Hom.: 11007 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.377 AC: 57370 AN: 152036 Hom.: 11023 Cov.: 32 AF XY: 0.379 AC XY: 28192 AN XY: 74318

African (AFR) AF: 0.319 AC: 13225 AN: 41470

American (AMR) AF: 0.451 AC: 6879 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2048 AN: 5164

South Asian (SAS) AF: 0.364 AC: 1754 AN: 4824

European-Finnish (FIN) AF: 0.395 AC: 4169 AN: 10566

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26930 AN: 67960

Other (OTH) AF: 0.380 AC: 802 AN: 2112

Alfa AF: 0.256 Hom.: 609

Bravo AF: 0.382

Asia WGS AF: 0.386 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.72
DANN	Benign	0.44
PhyloP100		-0.70

Splicing

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

Other links and lift over

dbSNP: rs844651; hg19: chr1-173225144;