rs12337739

Positions:

• chr9-114908384-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.239-2485T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,132 control chromosomes in the GnomAD database, including 26,741 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 0.57 (26741 hom., cov: 33)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF8	NM_001244.4	c.239-2485T>A		intron_variant		ENST00000223795.3	NP_001235.1
TNFSF8	NM_001252290.1	c.239-2485T>A		intron_variant			NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3	c.239-2485T>A		intron_variant		1	NM_001244.4	ENSP00000223795	P1
TNFSF8	ENST00000618336.4	c.239-2485T>A		intron_variant		3		ENSP00000484651
DELEC1	ENST00000648852.1	n.50-13066A>T		intron_variant, non_coding_transcript_variant
DELEC1	ENST00000649565.1	n.225+23076A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86751 AN: 152012 Hom.: 26685 Cov.: 33

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.571 AC: 86875 AN: 152132 Hom.: 26741 Cov.: 33 AF XY: 0.574 AC XY: 42658 AN XY: 74370

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.530

Alfa AF: 0.527 Hom.: 2810

Bravo AF: 0.595

Asia WGS AF: 0.517 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.84

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: rs12337739; hg19: chr9-117670664;