dbSNP rs12337739: TNFSF8:c.239-2485T>A (chr9-114908384-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001244.4(TNFSF8):c.239-2485T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,132 control chromosomes in the GnomAD database, including 26,741 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 0.57 ( 26741 hom., cov: 33)

Consequence

TNFSF8
NM_001244.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.197

Publications

6 publications found

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: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]

DELEC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF8	NM_001244.4 link	c.239-2485T>A		intron_variant	Intron 2 of 3	ENST00000223795.3	NP_001235.1	P32971Q52M88
TNFSF8	NM_001252290.1 link	c.239-2485T>A		intron_variant	Intron 2 of 4		NP_001239219.1	Q52M88A0A087X228

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3 link	c.239-2485T>A		intron_variant	Intron 2 of 3	1	NM_001244.4	ENSP00000223795.2		P32971

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86751

AN:

152012

Hom.:

26685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.799

Gnomad AMI

AF:

0.643

Gnomad AMR

AF:

0.647

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.527

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.571

AC:

86875

AN:

152132

Hom.:

26741

Cov.:

AF XY:

0.574

AC XY:

42658

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.799

AC:

33192

AN:

41516

American (AMR)

AF:

0.648

AC:

9902

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

1599

AN:

3470

East Asian (EAS)

AF:

0.404

AC:

2090

AN:

5170

South Asian (SAS)

AF:

0.450

AC:

2170

AN:

4822

European-Finnish (FIN)

AF:

0.505

AC:

5333

AN:

10570

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30765

AN:

67982

Other (OTH)

AF:

0.530

AC:

1118

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1794

3589

5383

7178

8972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.527

Hom.:

2810

Bravo

AF:

0.595

Asia WGS

AF:

0.517

AC:

1793

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over