rs6102287

Variant names:

• chr20-41116010-A-G
• rs6102287
• NM_003286.4:c.1708-268A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-41116010-A-G
• chr20-41116010-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003286.4(TOP1):​c.1708-268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,970 control chromosomes in the GnomAD database, including 25,236 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 0.56 (25236 hom., cov: 31)
• Consequence: TOP1 NM_003286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25
• Publications: 4 publications found

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]

PLCG1-AS1 (HGNC:40450): (PLCG1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOP1	NM_003286.4	c.1708-268A>G		intron_variant	Intron 16 of 20	ENST00000361337.3	NP_003277.1
PLCG1-AS1	NR_109889.1	n.711-14721T>C		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOP1	ENST00000361337.3	c.1708-268A>G		intron_variant	Intron 16 of 20	1	NM_003286.4	ENSP00000354522.2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85670 AN: 151852 Hom.: 25203 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.564 AC: 85762 AN: 151970 Hom.: 25236 Cov.: 31 AF XY: 0.566 AC XY: 42026 AN XY: 74278

African (AFR) AF: 0.721 AC: 29873 AN: 41458

American (AMR) AF: 0.540 AC: 8247 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1664 AN: 3468

East Asian (EAS) AF: 0.819 AC: 4234 AN: 5170

South Asian (SAS) AF: 0.487 AC: 2340 AN: 4800

European-Finnish (FIN) AF: 0.535 AC: 5654 AN: 10564

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32070 AN: 67908

Other (OTH) AF: 0.540 AC: 1141 AN: 2112

Alfa AF: 0.525 Hom.: 2694

Bravo AF: 0.575

Asia WGS AF: 0.624 AC: 2168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.20
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6102287; hg19: chr20-39744650;