Variant rs4082353 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_013432.5(TONSL):c.3943+215A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,056 control chromosomes in the GnomAD database, including 23,506 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 ( 23506 hom., cov: 33)

Consequence

TONSL
NM_013432.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00600

Variant links:

Genes affected

TONSL (HGNC:7801): (tonsoku like, DNA repair protein) The protein encoded by this gene is thought to be a negative regulator of NF-kappa-B mediated transcription. The encoded protein may bind NF-kappa-B complexes and trap them in the cytoplasm, preventing them from entering the nucleus and interacting with the DNA. Phosphorylation of this protein targets it for degradation by the ubiquitination pathway, which frees the NF-kappa-B complexes to enter the nucleus. [provided by RefSeq, Jul 2008]

TONSL links:

Genome browser will be placed here

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 (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TONSL	NM_013432.5 link	c.3943+215A>C	intron_variant	ENST00000409379.8	NP_038460.4	Q96HA7-1
TONSL	XM_011517048.3 link	c.2971+215A>C	intron_variant		XP_011515350.1
TONSL	XM_011517049.3 link	c.2935+215A>C	intron_variant		XP_011515351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TONSL	ENST00000409379.8 link	c.3943+215A>C		intron_variant		1	NM_013432.5	ENSP00000386239.3		Q96HA7-1
TONSL	ENST00000497613.2 link	n.6045+215A>C		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84123

AN:

151938

Hom.:

23479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.592

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.687

Gnomad EAS

AF:

0.586

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.544

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

GnomAD4 genome

AF:

0.554

AC:

84212

AN:

152056

Hom.:

23506

Cov.:

AF XY:

0.554

AC XY:

41161

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.593

Gnomad4 AMR

AF:

0.576

Gnomad4 ASJ

AF:

0.687

Gnomad4 EAS

AF:

0.587

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.524

Gnomad4 NFE

AF:

0.532

Gnomad4 OTH

AF:

0.545

Alfa

AF:

0.547

Hom.:

3276

Bravo

AF:

0.562

Asia WGS

AF:

0.489

AC:

1703

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

3.1

DANN

Benign

0.67

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.

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