rs9657980

chr1-7934973-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001561.6(TNFRSF9):c.544+40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,609,826 control chromosomes in the GnomAD database, including 466 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 0.015 (32 hom., cov: 32)
  • Exomes 𝑓: 0.022 (434 hom.)
• Consequence: TNFRSF9 NM_001561.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523

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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0151 (2295/152336) while in subpopulation NFE AF= 0.0262 (1782/68018). AF 95% confidence interval is 0.0252. There are 32 homozygotes in gnomad4. There are 1039 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF9	NM_001561.6	c.544+40T>C		intron_variant		ENST00000377507.8
TNFRSF9	XM_006710618.4	c.544+40T>C		intron_variant
TNFRSF9	XM_047419672.1	c.544+40T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF9	ENST00000377507.8	c.544+40T>C		intron_variant		1	NM_001561.6	P1
TNFRSF9	ENST00000474475.1	c.88+40T>C		intron_variant		3
TNFRSF9	ENST00000492571.1	c.*186+40T>C		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2296 AN: 152218 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.00432

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.0163 AC: 4037 AN: 247322 Hom.: 61 AF XY: 0.0161 AC XY: 2148 AN XY: 133642

Gnomad AFR exome AF: 0.00376

Gnomad AMR exome AF: 0.00443

Gnomad ASJ exome AF: 0.00371

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00904

Gnomad FIN exome AF: 0.0181

Gnomad NFE exome AF: 0.0271

Gnomad OTH exome AF: 0.0153

GnomAD4 exome AF: 0.0220 AC: 32112 AN: 1457490 Hom.: 434 Cov.: 30 AF XY: 0.0213 AC XY: 15426 AN XY: 724828

Gnomad4 AFR exome AF: 0.00327

Gnomad4 AMR exome AF: 0.00431

Gnomad4 ASJ exome AF: 0.00445

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.00978

Gnomad4 FIN exome AF: 0.0176

Gnomad4 NFE exome AF: 0.0260

Gnomad4 OTH exome AF: 0.0172

GnomAD4 genome AF: 0.0151 AC: 2295 AN: 152336 Hom.: 32 Cov.: 32 AF XY: 0.0139 AC XY: 1039 AN XY: 74502

Gnomad4 AFR AF: 0.00430

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00911

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.0262

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.0187 Hom.: 8

Bravo AF: 0.0137

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.072
Dann	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9657980; hg19: chr1-7995033;