rs3181357

chr9-114930064-G-Achr9-114930064-G-T

Variant summary

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

The NM_001244.4(TNFSF8):c.195+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 1,395,648 control chromosomes in the GnomAD database, including 14,214 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 0.21 (6922 hom., cov: 30)
  • Exomes 𝑓: 0.061 (7292 hom.)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF8	NM_001244.4	c.195+45C>T		intron_variant		ENST00000223795.3
TNFSF8	NM_001252290.1	c.195+45C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF8	ENST00000223795.3	c.195+45C>T		intron_variant		1	NM_001244.4	P1
TNFSF8	ENST00000618336.4	c.195+45C>T		intron_variant		3
DELEC1	ENST00000648852.1	n.198+8466G>A		intron_variant, non_coding_transcript_variant
DELEC1	ENST00000649565.1	n.226-39520G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31251 AN: 151432 Hom.: 6892 Cov.: 30

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0957

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.127 AC: 16826 AN: 132704 Hom.: 2742 AF XY: 0.105 AC XY: 7540 AN XY: 71502

Gnomad AFR exome AF: 0.565

Gnomad AMR exome AF: 0.335

Gnomad ASJ exome AF: 0.0349

Gnomad EAS exome AF: 0.140

Gnomad SAS exome AF: 0.0552

Gnomad FIN exome AF: 0.0932

Gnomad NFE exome AF: 0.0478

Gnomad OTH exome AF: 0.0962

GnomAD4 exome AF: 0.0612 AC: 76088 AN: 1244104 Hom.: 7292 Cov.: 25 AF XY: 0.0592 AC XY: 35820 AN XY: 605190

Gnomad4 AFR exome AF: 0.576

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.0377

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.0502

Gnomad4 FIN exome AF: 0.0943

Gnomad4 NFE exome AF: 0.0375

Gnomad4 OTH exome AF: 0.0831

GnomAD4 genome AF: 0.207 AC: 31339 AN: 151544 Hom.: 6922 Cov.: 30 AF XY: 0.206 AC XY: 15269 AN XY: 74010

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.0522

Gnomad4 FIN AF: 0.0957

Gnomad4 NFE AF: 0.0453

Gnomad4 OTH AF: 0.167

Alfa AF: 0.0711 Hom.: 364

Bravo AF: 0.235

Asia WGS AF: 0.126 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.6
Dann	Benign	0.79

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: rs3181357; hg19: chr9-117692344; COSMIC: COSV56342719;