rs732466

Variant names:

• chr22-21975375-G-A
• rs732466
• ENST00000458178.2:n.35595G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-21975375-G-A
• chr22-21975375-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000458178.2(PPM1F-AS1):​n.35595G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000469 in 213,288 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: PPM1F-AS1 ENST00000458178.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 0 publications found

Genes affected

PPM1F-AS1 (HGNC:40888): (PPM1F antisense RNA 1)

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000458178.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOP3B	NM_001282112.2	MANE Select	c.70+265C>T		intron	N/A	NP_001269041.1
	TOP3B	NM_001282113.2		c.70+265C>T		intron	N/A	NP_001269042.1
	TOP3B	NM_001349845.2		c.70+265C>T		intron	N/A	NP_001336774.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1F-AS1	ENST00000458178.2	TSL:1	n.35595G>A		non_coding_transcript_exon	Exon 2 of 2
	TOP3B	ENST00000357179.10	TSL:1 MANE Select	c.70+265C>T		intron	N/A	ENSP00000349705.5
	TOP3B	ENST00000398793.6	TSL:1	c.70+265C>T		intron	N/A	ENSP00000381773.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000469 AC: 1 AN: 213288 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 110994

African (AFR) AF: 0.00 AC: 0 AN: 6552

American (AMR) AF: 0.00 AC: 0 AN: 8764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7132

East Asian (EAS) AF: 0.00 AC: 0 AN: 15972

South Asian (SAS) AF: 0.00 AC: 0 AN: 16372

European-Finnish (FIN) AF: 0.0000720 AC: 1 AN: 13888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 996

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 130502

Other (OTH) AF: 0.00 AC: 0 AN: 13110

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.34
PhyloP100		-1.2

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

Other links and lift over

dbSNP: rs732466; hg19: chr22-22329747;