rs1322067

Variant names:

• chr9-114898653-A-G
• rs1322067
• NM_001252290.1:c.410-4489T>C

Variant summary

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

The NM_001252290.1(TNFSF8):​c.410-4489T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,984 control chromosomes in the GnomAD database, including 15,565 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 0.45 (15565 hom., cov: 32)
• Consequence: TNFSF8 NM_001252290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF8	NM_001252290.1	c.410-4489T>C		intron_variant	Intron 4 of 4		NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000618336.4	c.410-4489T>C		intron_variant	Intron 4 of 4	3		ENSP00000484651.1
TNFSF8	ENST00000474301.1	n.83-4489T>C		intron_variant	Intron 1 of 1	2
DELEC1	ENST00000648852.1	n.50-22797A>G		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67742 AN: 151864 Hom.: 15555 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.446 AC: 67786 AN: 151984 Hom.: 15565 Cov.: 32 AF XY: 0.452 AC XY: 33591 AN XY: 74290

African (AFR) AF: 0.393 AC: 16287 AN: 41444

American (AMR) AF: 0.600 AC: 9154 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1584 AN: 3472

East Asian (EAS) AF: 0.336 AC: 1734 AN: 5168

South Asian (SAS) AF: 0.435 AC: 2098 AN: 4824

European-Finnish (FIN) AF: 0.491 AC: 5184 AN: 10548

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30234 AN: 67944

Other (OTH) AF: 0.430 AC: 910 AN: 2114

Alfa AF: 0.457 Hom.: 20635

Bravo AF: 0.454

Asia WGS AF: 0.453 AC: 1569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		-0.39

Splicing

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

Other links and lift over

dbSNP: rs1322067; hg19: chr9-117660933;