dbSNP rs3181370: TNFSF8:c.*459A>G (chr9-114903472-T-C) – 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.*459A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 156,670 control chromosomes in the GnomAD database, including 10,877 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 ( 10493 hom., cov: 32)

Exomes 𝑓: 0.41 ( 384 hom. )

Consequence

TNFSF8
NM_001244.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

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=-1.02).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF8	NM_001244.4 link	c.*459A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000223795.3	NP_001235.1	P32971Q52M88
TNFSF8	NM_001252290.1 link	c.409+755A>G		intron_variant	Intron 4 of 4		NP_001239219.1	Q52M88A0A087X228

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3 link	c.*459A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_001244.4	ENSP00000223795.2		P32971

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

55011

AN:

151986

Hom.:

10482

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.404

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.357

GnomAD4 exome

AF:

0.409

AC:

1867

AN:

4568

Hom.:

384

Cov.:

AF XY:

0.412

AC XY:

964

AN XY:

2340

show subpopulations

African (AFR)

AF:

0.203

AC:

AN:

American (AMR)

AF:

0.425

AC:

114

AN:

268

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AF:

0.470

AC:

AN:

132

European-Finnish (FIN)

AF:

0.450

AC:

AN:

Middle Eastern (MID)

AF:

0.333

AC:

AN:

European-Non Finnish (NFE)

AF:

0.411

AC:

1571

AN:

3822

Other (OTH)

AF:

0.384

AC:

AN:

172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

112

167

223

279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.362

AC:

55046

AN:

152102

Hom.:

10493

Cov.:

AF XY:

0.365

AC XY:

27129

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.243

AC:

10091

AN:

41498

American (AMR)

AF:

0.453

AC:

6927

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

1453

AN:

3466

East Asian (EAS)

AF:

0.260

AC:

1342

AN:

5170

South Asian (SAS)

AF:

0.404

AC:

1948

AN:

4826

European-Finnish (FIN)

AF:

0.407

AC:

4296

AN:

10568

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.407

AC:

27694

AN:

67972

Other (OTH)

AF:

0.361

AC:

761

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1733

3466

5200

6933

8666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.394

Hom.:

5164

Bravo

AF:

0.358

Asia WGS

AF:

0.395

AC:

1369

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.1

(source)

DANN

Benign

0.17

PhyloP100

-1.1

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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rs3181370

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over