rs3181370

Variant names:

• chr9-114903472-T-C
• rs3181370
• NM_001244.4:c.*459A>G

Variant summary

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

The ENST00000223795.3(TNFSF8):​c.*459A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 156,670 control chromosomes in the GnomAD database, including 10,877 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 0.36 (10493 hom., cov: 32)
  • Exomes 𝑓: 0.41 (384 hom.)
• Consequence: TNFSF8 ENST00000223795.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 6 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000223795.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF8	NM_001244.4	MANE Select	c.*459A>G		3_prime_UTR	Exon 4 of 4	NP_001235.1
	TNFSF8	NM_001252290.1		c.409+755A>G		intron	N/A	NP_001239219.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF8	ENST00000223795.3	TSL:1 MANE Select	c.*459A>G		3_prime_UTR	Exon 4 of 4	ENSP00000223795.2
	TNFSF8	ENST00000618336.4	TSL:3	c.409+755A>G		intron	N/A	ENSP00000484651.1
	TNFSF8	ENST00000474301.1	TSL:2	n.82+755A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55011 AN: 151986 Hom.: 10482 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.357

GnomAD4 exome AF: 0.409 AC: 1867 AN: 4568 Hom.: 384 Cov.: 2 AF XY: 0.412 AC XY: 964 AN XY: 2340

African (AFR) AF: 0.203 AC: 15 AN: 74

American (AMR) AF: 0.425 AC: 114 AN: 268

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 14 AN: 32

East Asian (EAS) AF: 0.333 AC: 14 AN: 42

South Asian (SAS) AF: 0.470 AC: 62 AN: 132

European-Finnish (FIN) AF: 0.450 AC: 9 AN: 20

Middle Eastern (MID) AF: 0.333 AC: 2 AN: 6

European-Non Finnish (NFE) AF: 0.411 AC: 1571 AN: 3822

Other (OTH) AF: 0.384 AC: 66 AN: 172

GnomAD4 genome AF: 0.362 AC: 55046 AN: 152102 Hom.: 10493 Cov.: 32 AF XY: 0.365 AC XY: 27129 AN XY: 74344

African (AFR) AF: 0.243 AC: 10091 AN: 41498

American (AMR) AF: 0.453 AC: 6927 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3466

East Asian (EAS) AF: 0.260 AC: 1342 AN: 5170

South Asian (SAS) AF: 0.404 AC: 1948 AN: 4826

European-Finnish (FIN) AF: 0.407 AC: 4296 AN: 10568

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27694 AN: 67972

Other (OTH) AF: 0.361 AC: 761 AN: 2108

Alfa AF: 0.394 Hom.: 5164

Bravo AF: 0.358

Asia WGS AF: 0.395 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.17
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3181370; hg19: chr9-117665752;