chr9-114899385-C-A

Variant names:

• chr9-114899385-C-A
• rs7025577
• NM_001252290.1:c.409+4842G>T

Variant summary

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

The NM_001252290.1(TNFSF8):​c.409+4842G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 147,604 control chromosomes in the GnomAD database, including 25,402 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 (25402 hom., cov: 24)
• Consequence: TNFSF8 NM_001252290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF8	NM_001252290.1	c.409+4842G>T		intron_variant	Intron 4 of 4		NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000618336.4	c.409+4842G>T		intron_variant	Intron 4 of 4	3		ENSP00000484651.1
TNFSF8	ENST00000474301.1	n.82+4842G>T		intron_variant	Intron 1 of 1	2
DELEC1	ENST00000648852.1	n.50-22065C>A		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.564 AC: 83210 AN: 147496 Hom.: 25350 Cov.: 24

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.565 AC: 83326 AN: 147604 Hom.: 25402 Cov.: 24 AF XY: 0.567 AC XY: 40622 AN XY: 71660

African (AFR) AF: 0.797 AC: 31604 AN: 39678

American (AMR) AF: 0.641 AC: 9456 AN: 14748

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1587 AN: 3454

East Asian (EAS) AF: 0.400 AC: 2028 AN: 5068

South Asian (SAS) AF: 0.448 AC: 2094 AN: 4676

European-Finnish (FIN) AF: 0.486 AC: 4590 AN: 9452

Middle Eastern (MID) AF: 0.406 AC: 116 AN: 286

European-Non Finnish (NFE) AF: 0.449 AC: 30197 AN: 67284

Other (OTH) AF: 0.522 AC: 1073 AN: 2054

Alfa AF: 0.444 Hom.: 1696

Bravo AF: 0.593

Asia WGS AF: 0.516 AC: 1783 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.040
DANN	Benign	0.62
PhyloP100		-1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7025577; hg19: chr9-117661665;