rs519546

Positions:

• chr1-7941406-A-C

Variant summary

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

The ENST00000674210.1(TNFRSF9):​c.-234-473T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,034 control chromosomes in the GnomAD database, including 4,049 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 0.16 (4049 hom., cov: 32)
• Consequence: TNFRSF9 ENST00000674210.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

Genes affected

TNFRSF9 (HGNC:11924): (TNF receptor superfamily member 9) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contributes to the clonal expansion, survival, and development of T cells. It can also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation, and regulate CD28 co-stimulation to promote Th1 cell responses. The expression of this receptor is induced by lymphocyte activation. TRAF adaptor proteins have been shown to bind to this receptor and transduce the signals leading to activation of NF-kappaB. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF9	ENST00000674210.1	c.-234-473T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23682 AN: 151916 Hom.: 4038 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.0581

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.156 AC: 23736 AN: 152034 Hom.: 4049 Cov.: 32 AF XY: 0.158 AC XY: 11716 AN XY: 74372

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.0581

Gnomad4 FIN AF: 0.0131

Gnomad4 NFE AF: 0.0223

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0782 Hom.: 926

Bravo AF: 0.191

Asia WGS AF: 0.311 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.014
DANN	Benign	0.099

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: rs519546; hg19: chr1-8001466;