Variant 9-114905862-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001244.4(TNFSF8):c.276G>A(p.Arg92Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,607,498 control chromosomes in the GnomAD database, including 126,273 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 0.36 ( 10459 hom., cov: 31)

Exomes 𝑓: 0.40 ( 115814 hom. )

Consequence

TNFSF8
NM_001244.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Variant links:

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 links:

DELEC1 (HGNC:):

DELEC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP7

Synonymous conserved (PhyloP=-1.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF8	NM_001244.4 linkuse as main transcript	c.276G>A	p.Arg92Arg	synonymous_variant	3/4	ENST00000223795.3	NP_001235.1	P32971Q52M88
TNFSF8	NM_001252290.1 linkuse as main transcript	c.276G>A	p.Arg92Arg	synonymous_variant	3/5		NP_001239219.1	Q52M88A0A087X228

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TNFSF8	ENST00000223795.3 linkuse as main transcript	c.276G>A	p.Arg92Arg	synonymous_variant	3/4	1	NM_001244.4	ENSP00000223795.2	P32971
TNFSF8	ENST00000618336.4 linkuse as main transcript	c.276G>A	p.Arg92Arg	synonymous_variant	3/5	3		ENSP00000484651.1	A0A087X228
DELEC1	ENST00000648852.1 linkuse as main transcript	n.50-15588C>T		intron_variant
DELEC1	ENST00000649565.1 linkuse as main transcript	n.225+20554C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54891

AN:

151748

Hom.:

10448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.451

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.357

GnomAD3 exomes

AF:

0.388

AC:

97254

AN:

250464

Hom.:

19424

AF XY:

0.390

AC XY:

52767

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.438

Gnomad ASJ exome

AF:

0.439

Gnomad EAS exome

AF:

0.252

Gnomad SAS exome

AF:

0.398

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.406

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.396

AC:

576009

AN:

1455632

Hom.:

115814

Cov.:

AF XY:

0.396

AC XY:

286980

AN XY:

724452

show subpopulations

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.443

Gnomad4 ASJ exome

AF:

0.441

Gnomad4 EAS exome

AF:

0.310

Gnomad4 SAS exome

AF:

0.396

Gnomad4 FIN exome

AF:

0.401

Gnomad4 NFE exome

AF:

0.401

Gnomad4 OTH exome

AF:

0.386

GnomAD4 genome

AF:

0.362

AC:

54928

AN:

151866

Hom.:

10459

Cov.:

AF XY:

0.365

AC XY:

27065

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.243

Gnomad4 AMR

AF:

0.452

Gnomad4 ASJ

AF:

0.420

Gnomad4 EAS

AF:

0.260

Gnomad4 SAS

AF:

0.402

Gnomad4 FIN

AF:

0.407

Gnomad4 NFE

AF:

0.407

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.396

Hom.:

16059

Bravo

AF:

0.357

Asia WGS

AF:

0.393

AC:

1364

AN:

3478

EpiCase

AF:

0.399

EpiControl

AF:

0.403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.9

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over