rs2295800

chr9-114901931-T-C

Variant summary

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

The NM_001244.4(TNFSF8):c.*2000A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 981,390 control chromosomes in the GnomAD database, including 105,628 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 (24685 hom., cov: 33)
  • Exomes 𝑓: 0.44 (80943 hom.)
• Consequence: TNFSF8 NM_001244.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF8	NM_001244.4	c.*2000A>G		3_prime_UTR_variant	4/4	ENST00000223795.3
TNFSF8	NM_001252290.1	c.409+2296A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF8	ENST00000223795.3	c.*2000A>G		3_prime_UTR_variant	4/4	1	NM_001244.4	P1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83582 AN: 151942 Hom.: 24640 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.438 AC: 363291 AN: 829330 Hom.: 80943 Cov.: 18 AF XY: 0.437 AC XY: 167569 AN XY: 383176

Gnomad4 AFR exome AF: 0.788

Gnomad4 AMR exome AF: 0.690

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.550 AC: 83688 AN: 152060 Hom.: 24685 Cov.: 33 AF XY: 0.553 AC XY: 41093 AN XY: 74332

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.513

Alfa AF: 0.458 Hom.: 32790

Bravo AF: 0.573

Asia WGS AF: 0.483 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.5
Dann	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2295800; hg19: chr9-117664211;