rs3181367

Positions:

• chr9-114904398-G-A

Variant summary

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

The NM_001244.4(TNFSF8):​c.311-73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,514,676 control chromosomes in the GnomAD database, including 173,127 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 0.56 (25730 hom., cov: 32)
  • Exomes 𝑓: 0.46 (147397 hom.)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF8	NM_001244.4	c.311-73C>T		intron_variant		ENST00000223795.3
TNFSF8	NM_001252290.1	c.311-73C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF8	ENST00000223795.3	c.311-73C>T		intron_variant		1	NM_001244.4	P1
TNFSF8	ENST00000618336.4	c.311-73C>T		intron_variant		3
DELEC1	ENST00000648852.1	n.50-17052G>A		intron_variant, non_coding_transcript_variant
DELEC1	ENST00000649565.1	n.225+19090G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85386 AN: 151884 Hom.: 25681 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.458 AC: 624737 AN: 1362674 Hom.: 147397 AF XY: 0.457 AC XY: 305671 AN XY: 669308

Gnomad4 AFR exome AF: 0.789

Gnomad4 AMR exome AF: 0.723

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.487

Gnomad4 SAS exome AF: 0.446

Gnomad4 FIN exome AF: 0.497

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.471

GnomAD4 genome AF: 0.562 AC: 85500 AN: 152002 Hom.: 25730 Cov.: 32 AF XY: 0.565 AC XY: 42001 AN XY: 74274

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.526

Alfa AF: 0.522 Hom.: 3526

Bravo AF: 0.585

Asia WGS AF: 0.515 AC: 1783 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	0.69
DANN	Benign	0.66

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: rs3181367; hg19: chr9-117666678; COSMIC: COSV56342711; COSMIC: COSV56342711;