rs863171

chr1-7932555-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF9	NM_001561.6	c.679+607G>A		intron_variant		ENST00000377507.8
TNFRSF9	XM_006710618.4	c.679+607G>A		intron_variant
TNFRSF9	XM_047419672.1	c.680-425G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF9	ENST00000377507.8	c.679+607G>A		intron_variant		1	NM_001561.6	P1
TNFRSF9	ENST00000474475.1	c.223+607G>A		intron_variant		3

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

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.461

Alfa AF: 0.466 Hom.: 28684

Bravo AF: 0.407

Asia WGS AF: 0.500 AC: 1739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	7.6
Dann	Benign	0.65

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