rs2236876

Positions:

• chr1-173048346-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005092.4(TNFSF18):​c.156+2395C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,028 control chromosomes in the GnomAD database, including 9,001 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 0.32 (9001 hom., cov: 32)
• Consequence: TNFSF18 NM_005092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

Genes affected

TNFSF18 (HGNC:11932): (TNF superfamily member 18) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptor TNFRSF18/AITR/GITR. It has been shown to modulate T lymphocyte survival in peripheral tissues. This cytokine is also found to be expressed in endothelial cells, and is thought to be important for interaction between T lymphocytes and endothelial cells. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF18	NM_005092.4	c.156+2395C>T		intron_variant		ENST00000404377.5	NP_005083.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF18	ENST00000404377.5	c.156+2395C>T		intron_variant		1	NM_005092.4	ENSP00000385470	P1
	ENST00000432694.2	n.666-15527G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48802 AN: 151912 Hom.: 8992 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.321 AC: 48862 AN: 152028 Hom.: 9001 Cov.: 32 AF XY: 0.326 AC XY: 24245 AN XY: 74336

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.346

Alfa AF: 0.279 Hom.: 8259

Bravo AF: 0.337

Asia WGS AF: 0.630 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2236876; hg19: chr1-173017486;