Variant rs2242264 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013432.5(TONSL):c.865+15G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.986 in 1,611,010 control chromosomes in the GnomAD database, including 784,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 72830 hom., cov: 32)

Exomes 𝑓: 0.99 ( 711443 hom. )

Consequence

TONSL
NM_013432.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.79

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 8-144442022-C-G is Benign according to our data. Variant chr8-144442022-C-G is described in ClinVar as [Benign]. Clinvar id is 1167011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TONSL	NM_013432.5 linkuse as main transcript	c.865+15G>C	intron_variant	ENST00000409379.8
TONSL	XM_011517048.3 linkuse as main transcript	c.3+15G>C	intron_variant
TONSL	XM_011517049.3 linkuse as main transcript	c.3+15G>C	intron_variant
TONSL	XM_011517050.3 linkuse as main transcript	c.865+15G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TONSL	ENST00000409379.8 linkuse as main transcript	c.865+15G>C		intron_variant		1	NM_013432.5	P1	Q96HA7-1
TONSL	ENST00000497613.2 linkuse as main transcript	n.835G>C		non_coding_transcript_exon_variant	1/17	2

Frequencies

GnomAD3 genomes

AF:

0.977

AC:

148688

AN:

152120

Hom.:

72786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.976

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.929

Gnomad ASJ

AF:

0.989

Gnomad EAS

AF:

0.801

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

0.997

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.997

Gnomad OTH

AF:

0.977

GnomAD3 exomes

AF:

0.965

AC:

239412

AN:

248224

Hom.:

115988

AF XY:

0.971

AC XY:

131161

AN XY:

135146

show subpopulations

Gnomad AFR exome

AF:

0.976

Gnomad AMR exome

AF:

0.887

Gnomad ASJ exome

AF:

0.990

Gnomad EAS exome

AF:

0.789

Gnomad SAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.996

Gnomad NFE exome

AF:

0.997

Gnomad OTH exome

AF:

0.979

GnomAD4 exome

AF:

0.987

AC:

1439208

AN:

1458772

Hom.:

711443

Cov.:

AF XY:

0.987

AC XY:

716648

AN XY:

725734

show subpopulations

Gnomad4 AFR exome

AF:

0.978

Gnomad4 AMR exome

AF:

0.893

Gnomad4 ASJ exome

AF:

0.989

Gnomad4 EAS exome

AF:

0.756

Gnomad4 SAS exome

AF:

0.998

Gnomad4 FIN exome

AF:

0.995

Gnomad4 NFE exome

AF:

0.998

Gnomad4 OTH exome

AF:

0.986

GnomAD4 genome

AF:

0.977

AC:

148789

AN:

152238

Hom.:

72830

Cov.:

AF XY:

0.975

AC XY:

72566

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.976

Gnomad4 AMR

AF:

0.929

Gnomad4 ASJ

AF:

0.989

Gnomad4 EAS

AF:

0.800

Gnomad4 SAS

AF:

0.997

Gnomad4 FIN

AF:

0.997

Gnomad4 NFE

AF:

0.997

Gnomad4 OTH

AF:

0.977

Alfa

AF:

0.989

Hom.:

13682

Bravo

AF:

0.971

Asia WGS

AF:

0.936

AC:

3257

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Sponastrime dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.97

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over