rs6129731

Positions:

• chr20-41032047-A-C
• chr20-41032047-A-G
• chr20-41032047-A-T

Variant summary

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

The NM_003286.4(TOP1):​c.58+2592A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,032 control chromosomes in the GnomAD database, including 16,416 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 0.43 (16416 hom., cov: 32)
• Consequence: TOP1 NM_003286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873

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=-0.92).
• 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+2592A>C		intron_variant		ENST00000361337.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOP1	ENST00000361337.3	c.58+2592A>C		intron_variant		1	NM_003286.4	P1
TOP1	ENST00000681113.1	c.58+2592A>C		intron_variant, NMD_transcript_variant
TOP1	ENST00000681058.1	n.212+2592A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65886 AN: 151914 Hom.: 16388 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.434 AC: 65973 AN: 152032 Hom.: 16416 Cov.: 32 AF XY: 0.433 AC XY: 32207 AN XY: 74314

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.412

Alfa AF: 0.324 Hom.: 10333

Bravo AF: 0.455

Asia WGS AF: 0.609 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.45

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: rs6129731; hg19: chr20-39660687;