9-114903099-A-G

Position:

• chr9-114903099-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001244.4(TNFSF8):​c.*832T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,096 control chromosomes in the GnomAD database, including 24,930 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 (24924 hom., cov: 32)
  • Exomes 𝑓: 0.37 (6 hom.)
• Consequence: TNFSF8 NM_001244.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF8	NM_001244.4	c.*832T>C		3_prime_UTR_variant	4/4	ENST00000223795.3	NP_001235.1
TNFSF8	NM_001252290.1	c.409+1128T>C		intron_variant			NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3	c.*832T>C		3_prime_UTR_variant	4/4	1	NM_001244.4	ENSP00000223795.2

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84001 AN: 151922 Hom.: 24882 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.370 AC: 20 AN: 54 Hom.: 6 Cov.: 0 AF XY: 0.192 AC XY: 5 AN XY: 26

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.553 AC: 84102 AN: 152042 Hom.: 24924 Cov.: 32 AF XY: 0.555 AC XY: 41280 AN XY: 74312

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.516

Alfa AF: 0.477 Hom.: 6896

Bravo AF: 0.575

Asia WGS AF: 0.484 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.27
DANN	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs1126711; hg19: chr9-117665379;