rs3181372

chr9-114903155-A-Gchr9-114903155-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.*776T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,188 control chromosomes in the GnomAD database, including 26,798 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 (26786 hom., cov: 33)
  • Exomes 𝑓: 0.61 (12 hom.)
• Consequence: TNFSF8 NM_001244.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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=-1.06).
• 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	UniProt
TNFSF8	NM_001244.4	c.*776T>C		3_prime_UTR_variant	4/4	ENST00000223795.3
TNFSF8	NM_001252290.1	c.409+1072T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF8	ENST00000223795.3	c.*776T>C		3_prime_UTR_variant	4/4	1	NM_001244.4	P1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86840 AN: 152004 Hom.: 26730 Cov.: 33

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.609 AC: 39 AN: 64 Hom.: 12 Cov.: 0 AF XY: 0.595 AC XY: 25 AN XY: 42

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.596

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.572 AC: 86964 AN: 152124 Hom.: 26786 Cov.: 33 AF XY: 0.574 AC XY: 42699 AN XY: 74358

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.529

Alfa AF: 0.474 Hom.: 30112

Bravo AF: 0.595

Asia WGS AF: 0.519 AC: 1798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.24
Dann	Benign	0.20

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: rs3181372; hg19: chr9-117665435;