rs7036962

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001244.4(TNFSF8):​c.195+5238C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,984 control chromosomes in the GnomAD database, including 10,515 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 ( 10515 hom., cov: 32)

Consequence

TNFSF8
NM_001244.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.233
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNFSF8NM_001244.4 linkuse as main transcriptc.195+5238C>A intron_variant ENST00000223795.3 NP_001235.1 P32971Q52M88
TNFSF8NM_001252290.1 linkuse as main transcriptc.195+5238C>A intron_variant NP_001239219.1 Q52M88A0A087X228

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TNFSF8ENST00000223795.3 linkuse as main transcriptc.195+5238C>A intron_variant 1 NM_001244.4 ENSP00000223795.2 P32971
TNFSF8ENST00000618336.4 linkuse as main transcriptc.195+5238C>A intron_variant 3 ENSP00000484651.1 A0A087X228
DELEC1ENST00000648852.1 linkuse as main transcriptn.198+3273G>T intron_variant
DELEC1ENST00000649565.1 linkuse as main transcriptn.225+39563G>T intron_variant

Frequencies

GnomAD3 genomes
AF:
0.364
AC:
55217
AN:
151866
Hom.:
10504
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.253
Gnomad AMI
AF:
0.496
Gnomad AMR
AF:
0.453
Gnomad ASJ
AF:
0.418
Gnomad EAS
AF:
0.257
Gnomad SAS
AF:
0.387
Gnomad FIN
AF:
0.407
Gnomad MID
AF:
0.285
Gnomad NFE
AF:
0.407
Gnomad OTH
AF:
0.359
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.364
AC:
55255
AN:
151984
Hom.:
10515
Cov.:
32
AF XY:
0.366
AC XY:
27221
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.252
Gnomad4 AMR
AF:
0.454
Gnomad4 ASJ
AF:
0.418
Gnomad4 EAS
AF:
0.256
Gnomad4 SAS
AF:
0.387
Gnomad4 FIN
AF:
0.407
Gnomad4 NFE
AF:
0.406
Gnomad4 OTH
AF:
0.363
Alfa
AF:
0.379
Hom.:
1392
Bravo
AF:
0.360
Asia WGS
AF:
0.384
AC:
1332
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.96
DANN
Benign
0.42

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

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

Other links and lift over

dbSNP: rs7036962; hg19: chr9-117687151; API