chr1-173229990-G-T

Variant names:

• chr1-173229990-G-T
• rs6673550
• ENST00000714430.1:c.-10+9917C>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-10+9917C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,788 control chromosomes in the GnomAD database, including 31,943 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 0.63 (31943 hom., cov: 29)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 1 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF4	XM_047429896.1	c.148-22805C>A		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-22805C>A		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.-10+9917C>A		intron_variant	Intron 4 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-10+9917C>A		intron_variant	Intron 4 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-22805C>A		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95262 AN: 151670 Hom.: 31884 Cov.: 29

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.628 AC: 95383 AN: 151788 Hom.: 31943 Cov.: 29 AF XY: 0.628 AC XY: 46569 AN XY: 74164

African (AFR) AF: 0.871 AC: 36116 AN: 41444

American (AMR) AF: 0.653 AC: 9969 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1765 AN: 3462

East Asian (EAS) AF: 0.439 AC: 2262 AN: 5152

South Asian (SAS) AF: 0.503 AC: 2396 AN: 4768

European-Finnish (FIN) AF: 0.522 AC: 5485 AN: 10504

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35477 AN: 67882

Other (OTH) AF: 0.623 AC: 1317 AN: 2114

Alfa AF: 0.387 Hom.: 837

Bravo AF: 0.651

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.62
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs6673550; hg19: chr1-173199129;