NM_001244.4:c.196-1659C>G

Variant names:

• chr9-114919797-G-C
• rs7872878
• NM_001244.4:c.196-1659C>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.196-1659C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,976 control chromosomes in the GnomAD database, including 24,660 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 0.54 (24660 hom., cov: 31)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF8	NM_001244.4	MANE Select	c.196-1659C>G		intron	N/A	NP_001235.1	P32971
	TNFSF8	NM_001252290.1		c.196-1659C>G		intron	N/A	NP_001239219.1	A0A087X228

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF8	ENST00000223795.3	TSL:1 MANE Select	c.196-1659C>G		intron	N/A	ENSP00000223795.2	P32971
	TNFSF8	ENST00000872160.1		c.196-1659C>G		intron	N/A	ENSP00000542219.1
	TNFSF8	ENST00000618336.4	TSL:3	c.196-1659C>G		intron	N/A	ENSP00000484651.1	A0A087X228

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82652 AN: 151858 Hom.: 24609 Cov.: 31

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.545 AC: 82771 AN: 151976 Hom.: 24660 Cov.: 31 AF XY: 0.542 AC XY: 40280 AN XY: 74276

African (AFR) AF: 0.799 AC: 33151 AN: 41476

American (AMR) AF: 0.537 AC: 8207 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1569 AN: 3466

East Asian (EAS) AF: 0.257 AC: 1326 AN: 5166

South Asian (SAS) AF: 0.416 AC: 2002 AN: 4818

European-Finnish (FIN) AF: 0.438 AC: 4615 AN: 10534

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.446 AC: 30268 AN: 67934

Other (OTH) AF: 0.502 AC: 1061 AN: 2114

Alfa AF: 0.329 Hom.: 785

Bravo AF: 0.560

Asia WGS AF: 0.434 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		-0.095
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: rs7872878; hg19: chr9-117682077;