9-114919590-G-T

Variant names:

• chr9-114919590-G-T
• rs10982450
• NM_001244.4:c.196-1452C>A

Variant summary

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

The NM_001244.4(TNFSF8):​c.196-1452C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,992 control chromosomes in the GnomAD database, including 10,406 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 (10406 hom., cov: 32)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663
• Publications: 2 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=-0.87).
• 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.196-1452C>A		intron	N/A	NP_001235.1
	TNFSF8	NM_001252290.1		c.196-1452C>A		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.196-1452C>A		intron	N/A	ENSP00000223795.2
	TNFSF8	ENST00000618336.4	TSL:3	c.196-1452C>A		intron	N/A	ENSP00000484651.1
	DELEC1	ENST00000648852.1		n.50-1860G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54745 AN: 151874 Hom.: 10397 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.360 AC: 54779 AN: 151992 Hom.: 10406 Cov.: 32 AF XY: 0.363 AC XY: 26987 AN XY: 74280

African (AFR) AF: 0.242 AC: 10029 AN: 41450

American (AMR) AF: 0.453 AC: 6908 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1313 AN: 5164

South Asian (SAS) AF: 0.386 AC: 1855 AN: 4808

European-Finnish (FIN) AF: 0.408 AC: 4305 AN: 10562

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.406 AC: 27621 AN: 67968

Other (OTH) AF: 0.361 AC: 760 AN: 2108

Alfa AF: 0.241 Hom.: 612

Bravo AF: 0.357

Asia WGS AF: 0.380 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.61
PhyloP100		0.66
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: rs10982450; hg19: chr9-117681870;