rs7851560

Variant names:

• chr9-32545447-T-C
• rs7851560
• NM_005802.5:c.199-1121A>G

Variant summary

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

The NM_005802.5(TOPORS):​c.199-1121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 150,830 control chromosomes in the GnomAD database, including 4,288 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 0.23 (4288 hom., cov: 29)
• Consequence: TOPORS NM_005802.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 4 publications found

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

ENSG00000288684 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOPORS	NM_005802.5	c.199-1121A>G		intron_variant	Intron 2 of 2	ENST00000360538.7	NP_005793.2
TOPORS	NM_001195622.2	c.4-1121A>G		intron_variant	Intron 1 of 1		NP_001182551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOPORS	ENST00000360538.7	c.199-1121A>G		intron_variant	Intron 2 of 2	1	NM_005802.5	ENSP00000353735.2
TOPORS	ENST00000379858.1	c.4-1121A>G		intron_variant	Intron 1 of 1	1		ENSP00000369187.1
ENSG00000288684	ENST00000681750.1	c.-45+5327A>G		intron_variant	Intron 3 of 19			ENSP00000506413.1
ENSG00000288684	ENST00000680198.1	n.198+5327A>G		intron_variant	Intron 2 of 18			ENSP00000505143.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 34895 AN: 150712 Hom.: 4284 Cov.: 29

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.0964

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.231 AC: 34907 AN: 150830 Hom.: 4288 Cov.: 29 AF XY: 0.226 AC XY: 16651 AN XY: 73582

African (AFR) AF: 0.265 AC: 10872 AN: 40962

American (AMR) AF: 0.195 AC: 2941 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3464

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5174

South Asian (SAS) AF: 0.0967 AC: 462 AN: 4778

European-Finnish (FIN) AF: 0.215 AC: 2223 AN: 10332

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.252 AC: 17093 AN: 67764

Other (OTH) AF: 0.224 AC: 462 AN: 2066

Alfa AF: 0.250 Hom.: 728

Bravo AF: 0.231

Asia WGS AF: 0.0550 AC: 189 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	2.3
DANN	Benign	0.62
PhyloP100		-0.28
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: rs7851560; hg19: chr9-32545445; COSMIC: COSV62116505;