dbSNP rs628425: TOPORS:c.198+1170A>G (chr9-32549604-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005802.5(TOPORS):c.198+1170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,098 control chromosomes in the GnomAD database, including 6,499 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 0.27 ( 6499 hom., cov: 32)

Consequence

TOPORS
NM_005802.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.429

Publications

13 publications found

Variant links:

Genes affected

TOPORS (HGNC:21653): (TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase) This gene encodes a nuclear protein which is serine and arginine rich, and contains a RING-type zinc finger domain. It is highly expressed in the testis, and functions as an ubiquitin-protein E3 ligase. Mutations in this gene are associated with retinitis pigmentosa type 31. Alternatively spliced transcript variants, encoding different isoforms, have been observed for this locus. [provided by RefSeq, Sep 2010]

TOPORS Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa 31
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TOPORS links:

ENSG00000288684 (HGNC:):

ENSG00000288684 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOPORS	NM_005802.5 link	c.198+1170A>G		intron_variant	Intron 2 of 2	ENST00000360538.7	NP_005793.2	Q9NS56-1
TOPORS	NM_001195622.2 link	c.3+2830A>G		intron_variant	Intron 1 of 1		NP_001182551.1	Q9NS56-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TOPORS	ENST00000360538.7 link	c.198+1170A>G	intron_variant	Intron 2 of 2	1	NM_005802.5	ENSP00000353735.2	Q9NS56-1
TOPORS	ENST00000379858.1 link	c.3+2830A>G	intron_variant	Intron 1 of 1	1		ENSP00000369187.1	Q9NS56-2
ENSG00000288684	ENST00000681750.1 link	c.-45+1170A>G	intron_variant	Intron 3 of 19			ENSP00000506413.1	A0A7P0TB70
ENSG00000288684	ENST00000680198.1 link	n.198+1170A>G	intron_variant	Intron 2 of 18			ENSP00000505143.1	A0A7P0T8K8

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41625

AN:

151982

Hom.:

6490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.00481

Gnomad SAS

AF:

0.0973

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.259

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

GnomAD4 genome

AF:

0.274

AC:

41648

AN:

152098

Hom.:

6499

Cov.:

AF XY:

0.267

AC XY:

19866

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.417

AC:

17270

AN:

41434

American (AMR)

AF:

0.206

AC:

3155

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

603

AN:

3468

East Asian (EAS)

AF:

0.00482

AC:

AN:

5188

South Asian (SAS)

AF:

0.0976

AC:

471

AN:

4826

European-Finnish (FIN)

AF:

0.217

AC:

2297

AN:

10578

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.251

AC:

17064

AN:

67994

Other (OTH)

AF:

0.255

AC:

538

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1490

2981

4471

5962

7452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.247

Hom.:

2821

Bravo

AF:

0.278

Asia WGS

AF:

0.0640

AC:

221

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.6

(source)

DANN

Benign

0.49

PhyloP100

0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over