Menu
GeneBe

20-41061479-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_003286.4(TOP1):c.144G>A(p.Lys48=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.2 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 344 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TOP1NM_003286.4 linkuse as main transcriptc.144G>A p.Lys48= synonymous_variant 3/21 ENST00000361337.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TOP1ENST00000361337.3 linkuse as main transcriptc.144G>A p.Lys48= synonymous_variant 3/211 NM_003286.4 P1
TOP1ENST00000681058.1 linkuse as main transcriptn.298G>A non_coding_transcript_exon_variant 3/20
TOP1ENST00000681113.1 linkuse as main transcriptc.144G>A p.Lys48= synonymous_variant, NMD_transcript_variant 3/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00226
AC:
344
AN:
152194
Hom.:
1
Cov.:
32
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.:
1
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.:
13
Cov.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00226
AC:
344
AN:
152312
Hom.:
1
Cov.:
32
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.:
1
Bravo
AF:
0.00243
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 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.

Other links and lift over

dbSNP: rs35905808; hg19: chr20-39690119; API