rs3181374

chr9-114902907-A-Gchr9-114902907-A-T

Variant summary

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

The NM_001244.4(TNFSF8):c.*1024T>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 0.497 in 303,826 control chromosomes in the GnomAD database, including 40,418 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 0.55 (24952 hom., cov: 32)
  • Exomes 𝑓: 0.44 (15466 hom.)
• Consequence: TNFSF8 NM_001244.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF8	NM_001244.4	c.*1024T>C		3_prime_UTR_variant	4/4	ENST00000223795.3
TNFSF8	NM_001252290.1	c.409+1320T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF8	ENST00000223795.3	c.*1024T>C		3_prime_UTR_variant	4/4	1	NM_001244.4	P1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84038 AN: 151908 Hom.: 24907 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.439 AC: 66713 AN: 151798 Hom.: 15466 Cov.: 4 AF XY: 0.438 AC XY: 31833 AN XY: 72710

Gnomad4 AFR exome AF: 0.797

Gnomad4 AMR exome AF: 0.671

Gnomad4 ASJ exome AF: 0.498

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.476

Gnomad4 NFE exome AF: 0.433

Gnomad4 OTH exome AF: 0.435

GnomAD4 genome AF: 0.553 AC: 84141 AN: 152028 Hom.: 24952 Cov.: 32 AF XY: 0.556 AC XY: 41293 AN XY: 74316

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.516

Alfa AF: 0.522 Hom.: 3704

Bravo AF: 0.576

Asia WGS AF: 0.484 AC: 1676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.1
Dann	Benign	0.66

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: rs3181374; hg19: chr9-117665187;