rs732466

Positions:

• chr22-21975375-G-T

Variant summary

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

The NM_001282112.2(TOP3B):​c.70+265C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 364,850 control chromosomes in the GnomAD database, including 2,076 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 0.10 (863 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1213 hom.)
• Consequence: TOP3B NM_001282112.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

TOP3B (HGNC:11993): (DNA topoisomerase III beta) This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus relaxing the supercoils and altering the topology of DNA. The enzyme interacts with DNA helicase SGS1 and plays a role in DNA recombination, cellular aging and maintenance of genome stability. Low expression of this gene may be related to higher survival rates in breast cancer patients. This gene has a pseudogene on chromosome 22. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Aug 2013]

PPM1F-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOP3B	NM_001282112.2	c.70+265C>A		intron_variant		ENST00000357179.10	NP_001269041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOP3B	ENST00000357179.10	c.70+265C>A		intron_variant		1	NM_001282112.2	ENSP00000349705.5

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15738 AN: 151938 Hom.: 862 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0740

Gnomad SAS AF: 0.0494

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.103 AC: 21992 AN: 212794 Hom.: 1213 Cov.: 4 AF XY: 0.103 AC XY: 11397 AN XY: 110742

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.0917

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0673

Gnomad4 SAS exome AF: 0.0523

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.104 AC: 15745 AN: 152056 Hom.: 863 Cov.: 32 AF XY: 0.103 AC XY: 7627 AN XY: 74328

Gnomad4 AFR AF: 0.0759

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0739

Gnomad4 SAS AF: 0.0495

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.106

Alfa AF: 0.109 Hom.: 459

Bravo AF: 0.101

Asia WGS AF: 0.0760 AC: 265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.13
DANN	Benign	0.38

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: rs732466; hg19: chr22-22329747;