rs4082353

chr8-144430189-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
TONSL	NM_013432.5	c.3943+215A>C		intron_variant		ENST00000409379.8
TONSL	XM_011517048.3	c.2971+215A>C		intron_variant
TONSL	XM_011517049.3	c.2935+215A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TONSL	ENST00000409379.8	c.3943+215A>C		intron_variant		1	NM_013432.5	P1
TONSL	ENST00000497613.2	n.6045+215A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84123 AN: 151938 Hom.: 23479 Cov.: 33

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.: 33 AF XY: 0.554 AC XY: 41161 AN XY: 74304

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

Other links and lift over

dbSNP: rs4082353; hg19: chr8-145655572; COSMIC: COSV52873675; COSMIC: COSV52873675;