rs3181363

Variant names:

• chr9-114904962-C-T
• rs3181363
• NM_001244.4:c.311-637G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001244.4(TNFSF8):​c.311-637G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,026 control chromosomes in the GnomAD database, including 10,463 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 (10463 hom., cov: 33)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 3 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=-0.89).
• 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 rank	MANE	Protein	UniProt
TNFSF8	NM_001244.4	c.311-637G>A		intron_variant	Intron 3 of 3	ENST00000223795.3	NP_001235.1
TNFSF8	NM_001252290.1	c.311-637G>A		intron_variant	Intron 3 of 4		NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3	c.311-637G>A		intron_variant	Intron 3 of 3	1	NM_001244.4	ENSP00000223795.2

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54927 AN: 151908 Hom.: 10452 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.356

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.362 AC: 54964 AN: 152026 Hom.: 10463 Cov.: 33 AF XY: 0.365 AC XY: 27093 AN XY: 74316

African (AFR) AF: 0.243 AC: 10075 AN: 41462

American (AMR) AF: 0.453 AC: 6911 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1454 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1337 AN: 5162

South Asian (SAS) AF: 0.401 AC: 1936 AN: 4828

European-Finnish (FIN) AF: 0.407 AC: 4298 AN: 10554

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.407 AC: 27656 AN: 67970

Other (OTH) AF: 0.361 AC: 761 AN: 2110

Alfa AF: 0.374 Hom.: 1418

Bravo AF: 0.357

Asia WGS AF: 0.393 AC: 1363 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.19
DANN	Benign	0.55
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3181363; hg19: chr9-117667242;