rs519546

Variant names:

• chr1-7941406-A-C
• rs519546
• ENST00000674210.1:c.-234-473T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

TNFRSF9 Gene-Disease associations (from GenCC):

• immunodeficiency 109 with lymphoproliferation

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674210.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF9	ENST00000674210.1		c.-234-473T>G		intron	N/A	ENSP00000501326.1

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

African (AFR) AF: 0.361 AC: 14940 AN: 41438

American (AMR) AF: 0.246 AC: 3746 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3468

East Asian (EAS) AF: 0.514 AC: 2622 AN: 5106

South Asian (SAS) AF: 0.0581 AC: 280 AN: 4816

European-Finnish (FIN) AF: 0.0131 AC: 139 AN: 10620

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0223 AC: 1518 AN: 68016

Other (OTH) AF: 0.136 AC: 287 AN: 2108

Alfa AF: 0.111 Hom.: 2097

Bravo AF: 0.191

Asia WGS AF: 0.311 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.014
DANN	Benign	0.099
PhyloP100		-1.4

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

Other links and lift over

dbSNP: rs519546; hg19: chr1-8001466;