rs6072262

Variant names:

• chr20-41076355-G-A
• rs6072262
• NM_003286.4:c.279+61G>A

Variant summary

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

The NM_003286.4(TOP1):​c.279+61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,542,754 control chromosomes in the GnomAD database, including 16,905 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 0.13 (1417 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15488 hom.)
• Consequence: TOP1 NM_003286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOP1	NM_003286.4	c.279+61G>A		intron_variant	Intron 4 of 20	ENST00000361337.3	NP_003277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOP1	ENST00000361337.3	c.279+61G>A		intron_variant	Intron 4 of 20	1	NM_003286.4	ENSP00000354522.2
TOP1	ENST00000681392.1	n.173G>A		non_coding_transcript_exon_variant	Exon 1 of 18
TOP1	ENST00000681058.1	n.433+61G>A		intron_variant	Intron 4 of 19
TOP1	ENST00000681113.1	n.279+61G>A		intron_variant	Intron 4 of 22			ENSP00000505788.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19242 AN: 152088 Hom.: 1417 Cov.: 32

Gnomad AFR AF: 0.0780

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.143 AC: 198239 AN: 1390548 Hom.: 15488 AF XY: 0.140 AC XY: 96547 AN XY: 687790

Gnomad4 AFR exome AF: 0.0757

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.00593

Gnomad4 SAS exome AF: 0.0384

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.126 AC: 19248 AN: 152206 Hom.: 1417 Cov.: 32 AF XY: 0.128 AC XY: 9537 AN XY: 74426

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.00424

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.123

Alfa AF: 0.148 Hom.: 296

Bravo AF: 0.115

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.3
DANN	Benign	0.80

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: rs6072262; hg19: chr20-39704995;