rs4142394

Positions:

• chr20-41108082-T-C

Variant summary

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

The NM_003286.4(TOP1):​c.1309-4700T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,246 control chromosomes in the GnomAD database, including 2,134 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 0.12 (2134 hom., cov: 32)
• Consequence: TOP1 NM_003286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOP1	NM_003286.4	c.1309-4700T>C		intron_variant		ENST00000361337.3	NP_003277.1
PLCG1-AS1	NR_109889.1	n.711-6793A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOP1	ENST00000361337.3	c.1309-4700T>C		intron_variant		1	NM_003286.4	ENSP00000354522	P1
PLCG1-AS1	ENST00000454626.1	n.714-6793A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17844 AN: 152128 Hom.: 2131 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0972

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

GnomAD4 genome AF: 0.117 AC: 17876 AN: 152246 Hom.: 2134 Cov.: 32 AF XY: 0.120 AC XY: 8955 AN XY: 74446

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.0653

Gnomad4 FIN AF: 0.0538

Gnomad4 NFE AF: 0.0226

Gnomad4 OTH AF: 0.0962

Alfa AF: 0.0420 Hom.: 927

Bravo AF: 0.135

Asia WGS AF: 0.182 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.42

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: rs4142394; hg19: chr20-39736722;