rs741970

Positions:

• chr8-144443481-C-T

Variant summary

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

The NM_013432.5(TONSL):​c.265-160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 695,290 control chromosomes in the GnomAD database, including 962 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 0.021 (245 hom., cov: 33)
  • Exomes 𝑓: 0.018 (717 hom.)
• Consequence: TONSL NM_013432.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TONSL	NM_013432.5	c.265-160G>A		intron_variant		ENST00000409379.8	NP_038460.4
TONSL	XM_011517050.3	c.265-160G>A		intron_variant			XP_011515352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TONSL	ENST00000409379.8	c.265-160G>A		intron_variant		1	NM_013432.5	ENSP00000386239.3

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3270 AN: 152230 Hom.: 246 Cov.: 33

Gnomad AFR AF: 0.00294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.00583

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00229

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.0182 AC: 9889 AN: 542942 Hom.: 717 AF XY: 0.0173 AC XY: 4848 AN XY: 280856

Gnomad4 AFR exome AF: 0.00318

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.000562

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.00960

Gnomad4 FIN exome AF: 0.00450

Gnomad4 NFE exome AF: 0.00172

Gnomad4 OTH exome AF: 0.0185

GnomAD4 genome AF: 0.0214 AC: 3267 AN: 152348 Hom.: 245 Cov.: 33 AF XY: 0.0249 AC XY: 1858 AN XY: 74492

Gnomad4 AFR AF: 0.00293

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.0155

Gnomad4 FIN AF: 0.00583

Gnomad4 NFE AF: 0.00229

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.00845 Hom.: 9

Bravo AF: 0.0311

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.75

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: rs741970; hg19: chr8-145668864; COSMIC: COSV68048295; COSMIC: COSV68048295;