1-7920278-A-G

Position:

• chr1-7920278-A-G

Variant summary

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

The NM_001561.6(TNFRSF9):​c.*557T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 149,436 control chromosomes in the GnomAD database, including 7,038 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 0.20 (7038 hom., cov: 31)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: TNFRSF9 NM_001561.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF9	NM_001561.6	c.*557T>C		3_prime_UTR_variant	8/8	ENST00000377507.8	NP_001552.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF9	ENST00000377507	c.*557T>C		3_prime_UTR_variant	8/8	1	NM_001561.6	ENSP00000366729.3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30376 AN: 149160 Hom.: 7013 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.0610

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0710

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.0105 AC: 2 AN: 190 Hom.: 0 Cov.: 0 AF XY: 0.00943 AC XY: 1 AN XY: 106

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00725

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.204 AC: 30461 AN: 149246 Hom.: 7038 Cov.: 31 AF XY: 0.205 AC XY: 14894 AN XY: 72750

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.0610

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0231

Gnomad4 OTH AF: 0.172

Alfa AF: 0.0746 Hom.: 3048

Bravo AF: 0.245

Asia WGS AF: 0.327 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.50

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: rs161826; hg19: chr1-7980338;