9-114901604-G-T

Variant names:

• chr9-114901604-G-T
• rs3181200
• NM_001244.4:c.*2327C>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.*2327C>A 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 985,066 control chromosomes in the GnomAD database, including 105,822 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 (24632 hom., cov: 33)
  • Exomes 𝑓: 0.44 (81190 hom.)
• Consequence: TNFSF8 NM_001244.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.624
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF8	NM_001244.4	c.*2327C>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000223795.3	NP_001235.1
TNFSF8	NM_001252290.1	c.409+2623C>A		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.*2327C>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_001244.4	ENSP00000223795.2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83524 AN: 151966 Hom.: 24593 Cov.: 33

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.438 AC: 364837 AN: 832982 Hom.: 81190 Cov.: 33 AF XY: 0.437 AC XY: 168146 AN XY: 384658

African (AFR) AF: 0.787 AC: 12416 AN: 15786

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

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 2485 AN: 5150

East Asian (EAS) AF: 0.308 AC: 1117 AN: 3628

South Asian (SAS) AF: 0.440 AC: 7241 AN: 16456

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

Middle Eastern (MID) AF: 0.459 AC: 743 AN: 1620

European-Non Finnish (NFE) AF: 0.430 AC: 327942 AN: 761792

Other (OTH) AF: 0.443 AC: 12083 AN: 27290

GnomAD4 genome AF: 0.550 AC: 83622 AN: 152084 Hom.: 24632 Cov.: 33 AF XY: 0.552 AC XY: 41066 AN XY: 74338

African (AFR) AF: 0.752 AC: 31198 AN: 41500

American (AMR) AF: 0.640 AC: 9784 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1597 AN: 3470

East Asian (EAS) AF: 0.339 AC: 1747 AN: 5156

South Asian (SAS) AF: 0.436 AC: 2100 AN: 4822

European-Finnish (FIN) AF: 0.492 AC: 5190 AN: 10554

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

European-Non Finnish (NFE) AF: 0.447 AC: 30349 AN: 67968

Other (OTH) AF: 0.512 AC: 1084 AN: 2116

Alfa AF: 0.507 Hom.: 7947

Bravo AF: 0.572

Asia WGS AF: 0.482 AC: 1669 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.5
DANN	Benign	0.62
PhyloP100		0.62

Splicing

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

Other links and lift over

dbSNP: rs3181200; hg19: chr9-117663884;