9-114901604-G-T

Position:

• chr9-114901604-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

TNFSF8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TNFSF8	NM_001244.4	c.*2327C>A		3_prime_UTR_variant	4/4	ENST00000223795.3	NP_001235.1
TNFSF8	NM_001252290.1	c.409+2623C>A		intron_variant			NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3	c.*2327C>A		3_prime_UTR_variant	4/4	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

Gnomad4 AFR exome AF: 0.787

Gnomad4 AMR exome AF: 0.690

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.308

Gnomad4 SAS exome AF: 0.440

Gnomad4 FIN exome AF: 0.475

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.443

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

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.512

Alfa AF: 0.507 Hom.: 5112

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3181200; hg19: chr9-117663884;