Variant 20-41061479-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_003286.4(TOP1):c.144G>A(p.Lys48Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,599,296 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 13 hom. )

Consequence

TOP1
NM_003286.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.20

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:

TOP1 (HGNC:):

TOP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 20-41061479-G-A is Benign according to our data. Variant chr20-41061479-G-A is described in ClinVar as [Benign]. Clinvar id is 708476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.2 with no splicing effect.

BS2

High AC in GnomAd4 at 344 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOP1	NM_003286.4 linkuse as main transcript	c.144G>A	p.Lys48Lys	synonymous_variant	3/21	ENST00000361337.3	NP_003277.1	P11387Q9BVT2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TOP1	ENST00000361337.3 linkuse as main transcript	c.144G>A	p.Lys48Lys	synonymous_variant	3/21	1	NM_003286.4	ENSP00000354522.2	P11387
TOP1	ENST00000681058.1 linkuse as main transcript	n.298G>A		non_coding_transcript_exon_variant	3/20
TOP1	ENST00000681113.1 linkuse as main transcript	n.144G>A		non_coding_transcript_exon_variant	3/23			ENSP00000505788.1	A0A7P0T9R7

Frequencies

GnomAD3 genomes

AF:

0.00226

AC:

344

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00398

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00249

AC:

549

AN:

220558

Hom.:

AF XY:

0.00266

AC XY:

317

AN XY:

119158

show subpopulations

Gnomad AFR exome

AF:

0.000573

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.0000620

Gnomad SAS exome

AF:

0.00178

Gnomad FIN exome

AF:

0.000874

Gnomad NFE exome

AF:

0.00416

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00366

AC:

5300

AN:

1446984

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

2616

AN XY:

718604

show subpopulations

Gnomad4 AFR exome

AF:

0.000634

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.00310

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00176

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.00431

Gnomad4 OTH exome

AF:

0.00293

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152312

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

155

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00398

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00353

Hom.:

Bravo

AF:

0.00243

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.0

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over