rs2620660

chr8-144443681-G-Achr8-144443681-G-T

Variant summary

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

The NM_013432.5(TONSL):c.264+201C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 152,264 control chromosomes in the GnomAD database, including 1,232 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 0.069 (1232 hom., cov: 33)
• Consequence: TONSL NM_013432.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TONSL	NM_013432.5	c.264+201C>T		intron_variant		ENST00000409379.8
TONSL	XM_011517050.3	c.264+201C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TONSL	ENST00000409379.8	c.264+201C>T		intron_variant		1	NM_013432.5	P1

Frequencies

GnomAD3 genomes AF: 0.0692 AC: 10525 AN: 152146 Hom.: 1227 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.0516

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

GnomAD4 genome AF: 0.0692 AC: 10542 AN: 152264 Hom.: 1232 Cov.: 33 AF XY: 0.0670 AC XY: 4988 AN XY: 74438

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.0256

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000661

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.00411 Hom.: 5

Bravo AF: 0.0800

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	7.5
Dann	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2620660; hg19: chr8-145669064;