rs3181369

Positions:

• chr9-114903586-G-A
• chr9-114903586-G-C

Variant summary

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

The NM_001244.4(TNFSF8):​c.*345C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 542,922 control chromosomes in the GnomAD database, including 41,789 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 0.36 (10493 hom., cov: 33)
  • Exomes 𝑓: 0.40 (31296 hom.)
• Consequence: TNFSF8 NM_001244.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664

Genes affected

TNFSF8 (HGNC:11938): (TNF superfamily member 8) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for TNFRSF8/CD30, which is a cell surface antigen and a marker for Hodgkin lymphoma and related hematologic malignancies. The engagement of this cytokine expressed on B cell surface plays an inhibitory role in modulating Ig class switch. This cytokine was shown to enhance cell proliferation of some lymphoma cell lines, while to induce cell death and reduce cell proliferation of other lymphoma cell lines. The pleiotropic biologic activities of this cytokine on different CD30+ lymphoma cell lines may play a pathophysiologic role in Hodgkin's and some non-Hodgkin's lymphomas. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

DELEC1 (HGNC:23658): (deleted in esophageal cancer 1) The function of this gene is not known. This gene is located in a region commonly deleted in esophageal squamous cell carcinomas. Gene expression is reduced or absent in these carcinomas and thus this is a candidate tumor suppressor gene for esophageal squamous cell carcinomas. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF8	NM_001244.4	c.*345C>T		3_prime_UTR_variant	4/4	ENST00000223795.3
TNFSF8	NM_001252290.1	c.409+641C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF8	ENST00000223795.3	c.*345C>T		3_prime_UTR_variant	4/4	1	NM_001244.4	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54998 AN: 151950 Hom.: 10482 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.357

GnomAD4 exome AF: 0.397 AC: 155234 AN: 390854 Hom.: 31296 Cov.: 6 AF XY: 0.397 AC XY: 73593 AN XY: 185356

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.435

Gnomad4 ASJ exome AF: 0.436

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.402

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.362 AC: 55034 AN: 152068 Hom.: 10493 Cov.: 33 AF XY: 0.365 AC XY: 27133 AN XY: 74324

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.362

Alfa AF: 0.399 Hom.: 18356

Bravo AF: 0.357

Asia WGS AF: 0.395 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Benign	0.80

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: rs3181369; hg19: chr9-117665866;