rs3181367

Variant names:

• chr9-114904398-G-A
• rs3181367
• NM_001244.4:c.311-73C>T

Variant summary

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244.4. 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.311-73C>T		intron	N/A	NP_001235.1
	TNFSF8	NM_001252290.1		c.311-73C>T		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.311-73C>T		intron	N/A	ENSP00000223795.2
	TNFSF8	ENST00000618336.4	TSL:3	c.311-73C>T		intron	N/A	ENSP00000484651.1
	DELEC1	ENST00000648852.1		n.50-17052G>A		intron	N/A

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

African (AFR) AF: 0.789 AC: 23854 AN: 30224

American (AMR) AF: 0.723 AC: 21144 AN: 29250

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 9662 AN: 20094

East Asian (EAS) AF: 0.487 AC: 19023 AN: 39022

South Asian (SAS) AF: 0.446 AC: 30854 AN: 69114

European-Finnish (FIN) AF: 0.497 AC: 22587 AN: 45484

Middle Eastern (MID) AF: 0.433 AC: 2163 AN: 5000

European-Non Finnish (NFE) AF: 0.439 AC: 468977 AN: 1068236

Other (OTH) AF: 0.471 AC: 26473 AN: 56250

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

African (AFR) AF: 0.770 AC: 31944 AN: 41476

American (AMR) AF: 0.645 AC: 9857 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1599 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2089 AN: 5158

South Asian (SAS) AF: 0.451 AC: 2175 AN: 4820

European-Finnish (FIN) AF: 0.504 AC: 5321 AN: 10554

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30698 AN: 67930

Other (OTH) AF: 0.526 AC: 1109 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.66
PhyloP100		-0.68
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: rs3181367; hg19: chr9-117666678; COSMIC: COSV56342711; COSMIC: COSV56342711;