rs2295800

Variant names:

• chr9-114901931-T-C
• rs2295800
• NM_001244.4:c.*2000A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNFSF8	NM_001244.4	c.*2000A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000223795.3	NP_001235.1
TNFSF8	NM_001252290.1	c.409+2296A>G		intron_variant	Intron 4 of 4		NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3	c.*2000A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_001244.4	ENSP00000223795.2

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

African (AFR) AF: 0.788 AC: 12378 AN: 15704

American (AMR) AF: 0.690 AC: 675 AN: 978

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 2471 AN: 5124

East Asian (EAS) AF: 0.307 AC: 1109 AN: 3608

South Asian (SAS) AF: 0.441 AC: 7230 AN: 16394

European-Finnish (FIN) AF: 0.478 AC: 131 AN: 274

Middle Eastern (MID) AF: 0.460 AC: 740 AN: 1608

European-Non Finnish (NFE) AF: 0.430 AC: 326513 AN: 758472

Other (OTH) AF: 0.443 AC: 12044 AN: 27168

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

African (AFR) AF: 0.753 AC: 31238 AN: 41464

American (AMR) AF: 0.640 AC: 9778 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1598 AN: 3470

East Asian (EAS) AF: 0.340 AC: 1754 AN: 5166

South Asian (SAS) AF: 0.437 AC: 2107 AN: 4824

European-Finnish (FIN) AF: 0.491 AC: 5180 AN: 10552

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30377 AN: 67984

Other (OTH) AF: 0.513 AC: 1083 AN: 2110

Alfa AF: 0.478 Hom.: 75333

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
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs2295800; hg19: chr9-117664211;