20-41115779-A-C

Variant names:

• chr20-41115779-A-C
• rs2235362
• NM_003286.4:c.1707+340A>C

Variant summary

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

The NM_003286.4(TOP1):​c.1707+340A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,104 control chromosomes in the GnomAD database, including 3,660 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 0.19 (3660 hom., cov: 32)
• Consequence: TOP1 NM_003286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 1 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOP1	NM_003286.4	c.1707+340A>C		intron_variant	Intron 16 of 20	ENST00000361337.3	NP_003277.1
PLCG1-AS1	NR_109889.1	n.711-14490T>G		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOP1	ENST00000361337.3	c.1707+340A>C		intron_variant	Intron 16 of 20	1	NM_003286.4	ENSP00000354522.2

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28760 AN: 151986 Hom.: 3649 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.189 AC: 28797 AN: 152104 Hom.: 3660 Cov.: 32 AF XY: 0.194 AC XY: 14449 AN XY: 74370

African (AFR) AF: 0.123 AC: 5085 AN: 41494

American (AMR) AF: 0.255 AC: 3900 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 332 AN: 3470

East Asian (EAS) AF: 0.705 AC: 3633 AN: 5150

South Asian (SAS) AF: 0.314 AC: 1514 AN: 4814

European-Finnish (FIN) AF: 0.147 AC: 1562 AN: 10600

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12176 AN: 67976

Other (OTH) AF: 0.190 AC: 400 AN: 2110

Alfa AF: 0.182 Hom.: 3382

Bravo AF: 0.198

Asia WGS AF: 0.429 AC: 1490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		-0.12
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: rs2235362; hg19: chr20-39744419;