Genetic Variant NM_001244.4:c.*832T>C (chr9-114903099-A-G) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.18

Publications

7 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=-1.06).

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 rank	MANE	Protein	UniProt
TNFSF8	NM_001244.4 link	c.*832T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000223795.3	NP_001235.1	P32971Q52M88
TNFSF8	NM_001252290.1 link	c.409+1128T>C		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.*832T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001244.4	ENSP00000223795.2		P32971

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

84001

AN:

151922

Hom.:

24882

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.192

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.295

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.553

AC:

84102

AN:

152042

Hom.:

24924

Cov.:

AF XY:

0.555

AC XY:

41280

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.756

AC:

31384

AN:

41504

American (AMR)

AF:

0.643

AC:

9825

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

1603

AN:

3472

East Asian (EAS)

AF:

0.339

AC:

1747

AN:

5154

South Asian (SAS)

AF:

0.437

AC:

2105

AN:

4822

European-Finnish (FIN)

AF:

0.493

AC:

5203

AN:

10550

Middle Eastern (MID)

AF:

0.408

AC:

119

AN:

292

European-Non Finnish (NFE)

AF:

0.450

AC:

30576

AN:

67940

Other (OTH)

AF:

0.516

AC:

1088

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1770

3539

5309

7078

8848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.485

Hom.:

8516

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

(source)

DANN

Benign

0.26

PhyloP100

-2.2

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