9-114915025-A-C

Variant names:

• chr9-114915025-A-C
• rs4978611
• NM_001244.4:c.238+3071T>G

Variant summary

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

The NM_001244.4(TNFSF8):​c.238+3071T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,042 control chromosomes in the GnomAD database, including 25,858 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 (25858 hom., cov: 32)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 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.238+3071T>G		intron	N/A	NP_001235.1
	TNFSF8	NM_001252290.1		c.238+3071T>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.238+3071T>G		intron	N/A	ENSP00000223795.2
	TNFSF8	ENST00000618336.4	TSL:3	c.238+3071T>G		intron	N/A	ENSP00000484651.1
	DELEC1	ENST00000648852.1		n.50-6425A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85529 AN: 151924 Hom.: 25805 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.563 AC: 85649 AN: 152042 Hom.: 25858 Cov.: 32 AF XY: 0.566 AC XY: 42055 AN XY: 74304

African (AFR) AF: 0.775 AC: 32163 AN: 41500

American (AMR) AF: 0.646 AC: 9867 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1596 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2086 AN: 5148

South Asian (SAS) AF: 0.436 AC: 2099 AN: 4818

European-Finnish (FIN) AF: 0.503 AC: 5313 AN: 10560

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.452 AC: 30706 AN: 67948

Other (OTH) AF: 0.526 AC: 1111 AN: 2112

Alfa AF: 0.530 Hom.: 3783

Bravo AF: 0.586

Asia WGS AF: 0.506 AC: 1755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.80
PhyloP100		-0.080
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: rs4978611; hg19: chr9-117677305;