rs6029526

chr20-41043978-T-Achr20-41043978-T-Cchr20-41043978-T-G

Variant summary

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

The NM_003286.4(TOP1):c.58+14523T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,174 control chromosomes in the GnomAD database, including 27,353 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 0.58 (27353 hom., cov: 33)
• Consequence: TOP1 NM_003286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599

Genes affected

TOP1 (HGNC:11986): (DNA topoisomerase I) 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 altering the topology of DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOP1	NM_003286.4	c.58+14523T>A		intron_variant		ENST00000361337.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOP1	ENST00000361337.3	c.58+14523T>A		intron_variant		1	NM_003286.4	P1
TOP1	ENST00000681113.1	c.58+14523T>A		intron_variant, NMD_transcript_variant
TOP1	ENST00000681058.1	n.212+14523T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88512 AN: 152056 Hom.: 27309 Cov.: 33

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.582 AC: 88622 AN: 152174 Hom.: 27353 Cov.: 33 AF XY: 0.583 AC XY: 43354 AN XY: 74394

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.553

Alfa AF: 0.506 Hom.: 11447

Bravo AF: 0.593

Asia WGS AF: 0.643 AC: 2236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.72
Dann	Benign	0.52

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: rs6029526; hg19: chr20-39672618;