9-114904496-G-A

Variant names:

• chr9-114904496-G-A
• rs3181366
• NM_001244.4:c.311-171C>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.311-171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,988 control chromosomes in the GnomAD database, including 10,473 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 (10473 hom., cov: 32)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 10 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=-0.85).
• 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: 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.311-171C>T		intron	N/A	NP_001235.1
	TNFSF8	NM_001252290.1		c.311-171C>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.311-171C>T		intron	N/A	ENSP00000223795.2
	TNFSF8	ENST00000618336.4	TSL:3	c.311-171C>T		intron	N/A	ENSP00000484651.1
	DELEC1	ENST00000648852.1		n.50-16954G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54944 AN: 151870 Hom.: 10462 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.358

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.362 AC: 54981 AN: 151988 Hom.: 10473 Cov.: 32 AF XY: 0.365 AC XY: 27097 AN XY: 74280

African (AFR) AF: 0.243 AC: 10074 AN: 41450

American (AMR) AF: 0.453 AC: 6914 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1454 AN: 3466

East Asian (EAS) AF: 0.260 AC: 1344 AN: 5170

South Asian (SAS) AF: 0.402 AC: 1934 AN: 4816

European-Finnish (FIN) AF: 0.408 AC: 4302 AN: 10548

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

European-Non Finnish (NFE) AF: 0.407 AC: 27660 AN: 67964

Other (OTH) AF: 0.362 AC: 763 AN: 2108

Alfa AF: 0.395 Hom.: 6037

Bravo AF: 0.357

Asia WGS AF: 0.394 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.54
PhyloP100		0.21
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: rs3181366; hg19: chr9-117666776;