rs863171

Variant names:

• chr1-7932555-C-T
• rs863171
• NM_001561.6:c.679+607G>A

Variant summary

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

The NM_001561.6(TNFRSF9):​c.679+607G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,934 control chromosomes in the GnomAD database, including 14,135 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 0.42 (14135 hom., cov: 31)
• Consequence: TNFRSF9 NM_001561.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• Publications: 10 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: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, ClinGen, 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001561.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF9	NM_001561.6	MANE Select	c.679+607G>A		intron	N/A	NP_001552.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF9	ENST00000377507.8	TSL:1 MANE Select	c.679+607G>A		intron	N/A	ENSP00000366729.3	Q07011
	TNFRSF9	ENST00000875592.1		c.679+607G>A		intron	N/A	ENSP00000545651.1
	TNFRSF9	ENST00000474475.1	TSL:3	c.223+607G>A		intron	N/A	ENSP00000465272.1	K7EJQ2

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63800 AN: 151816 Hom.: 14133 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.420 AC: 63821 AN: 151934 Hom.: 14135 Cov.: 31 AF XY: 0.423 AC XY: 31393 AN XY: 74216

African (AFR) AF: 0.288 AC: 11924 AN: 41434

American (AMR) AF: 0.420 AC: 6416 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2167 AN: 5154

South Asian (SAS) AF: 0.630 AC: 3033 AN: 4814

European-Finnish (FIN) AF: 0.429 AC: 4512 AN: 10520

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32444 AN: 67966

Other (OTH) AF: 0.461 AC: 970 AN: 2106

Alfa AF: 0.453 Hom.: 44134

Bravo AF: 0.407

Asia WGS AF: 0.500 AC: 1739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.6
DANN	Benign	0.65
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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: rs863171; hg19: chr1-7992615; COSMIC: COSV66348933; COSMIC: COSV66348933;