chr9-114901520-G-C

Variant names:

• chr9-114901520-G-C
• rs3181201
• NM_001244.4:c.*2411C>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.*2411C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 984,978 control chromosomes in the GnomAD database, including 105,795 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 0.55 (24604 hom., cov: 32)
  • Exomes 𝑓: 0.44 (81191 hom.)
• Consequence: TNFSF8 NM_001244.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF8	NM_001244.4	c.*2411C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000223795.3	NP_001235.1
TNFSF8	NM_001252290.1	c.409+2707C>G		intron_variant	Intron 4 of 4		NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3	c.*2411C>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_001244.4	ENSP00000223795.2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83473 AN: 151846 Hom.: 24567 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.438 AC: 364871 AN: 833016 Hom.: 81191 Cov.: 33 AF XY: 0.437 AC XY: 168167 AN XY: 384668

African (AFR) AF: 0.786 AC: 12403 AN: 15782

American (AMR) AF: 0.690 AC: 679 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 2486 AN: 5152

East Asian (EAS) AF: 0.308 AC: 1119 AN: 3630

South Asian (SAS) AF: 0.441 AC: 7255 AN: 16460

European-Finnish (FIN) AF: 0.475 AC: 131 AN: 276

Middle Eastern (MID) AF: 0.458 AC: 742 AN: 1620

European-Non Finnish (NFE) AF: 0.431 AC: 327968 AN: 761816

Other (OTH) AF: 0.443 AC: 12088 AN: 27296

GnomAD4 genome AF: 0.550 AC: 83569 AN: 151962 Hom.: 24604 Cov.: 32 AF XY: 0.552 AC XY: 41025 AN XY: 74262

African (AFR) AF: 0.751 AC: 31141 AN: 41470

American (AMR) AF: 0.640 AC: 9781 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1595 AN: 3462

East Asian (EAS) AF: 0.340 AC: 1757 AN: 5172

South Asian (SAS) AF: 0.437 AC: 2106 AN: 4820

European-Finnish (FIN) AF: 0.491 AC: 5174 AN: 10530

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30365 AN: 67920

Other (OTH) AF: 0.512 AC: 1080 AN: 2110

Alfa AF: 0.513 Hom.: 2643

Bravo AF: 0.572

Asia WGS AF: 0.482 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.62
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs3181201; hg19: chr9-117663800;