dbSNP rs6072262: TOP1:c.279+61G>A (chr20-41076355-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Publications

13 publications found

Variant links:

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]

TOP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003286.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOP1	NM_003286.4	MANE Select	c.279+61G>A		intron	N/A	NP_003277.1	P11387

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TOP1	ENST00000361337.3	TSL:1 MANE Select	c.279+61G>A	intron	N/A	ENSP00000354522.2	P11387
TOP1	ENST00000681392.1		n.173G>A	non_coding_transcript_exon	Exon 1 of 18
TOP1	ENST00000681058.1		n.433+61G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19242

AN:

152088

Hom.:

1417

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0757

AC:

2323

AN:

30672

American (AMR)

AF:

0.127

AC:

4244

AN:

33504

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

3240

AN:

22624

East Asian (EAS)

AF:

0.00593

AC:

229

AN:

38608

South Asian (SAS)

AF:

0.0384

AC:

2860

AN:

74452

European-Finnish (FIN)

AF:

0.249

AC:

12199

AN:

49072

Middle Eastern (MID)

AF:

0.108

AC:

581

AN:

5404

European-Non Finnish (NFE)

AF:

0.153

AC:

165362

AN:

1079088

Other (OTH)

AF:

0.126

AC:

7201

AN:

57124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

6939

13877

20816

27754

34693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5848

11696

17544

23392

29240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.126

AC:

19248

AN:

152206

Hom.:

1417

Cov.:

AF XY:

0.128

AC XY:

9537

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0780

AC:

3239

AN:

41536

American (AMR)

AF:

0.117

AC:

1794

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

452

AN:

3472

East Asian (EAS)

AF:

0.00424

AC:

AN:

5184

South Asian (SAS)

AF:

0.0361

AC:

174

AN:

4822

European-Finnish (FIN)

AF:

0.252

AC:

2667

AN:

10586

Middle Eastern (MID)

AF:

0.0993

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.155

AC:

10506

AN:

67992

Other (OTH)

AF:

0.123

AC:

261

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

838

1676

2514

3352

4190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.138

Hom.:

2536

Bravo

AF:

0.115

Asia WGS

AF:

0.0290

AC:

102

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.3

(source)

DANN

Benign

0.80

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over