rs280026

Variant names:

• chr15-76739589-C-T
• rs280026
• NM_020843.4:c.1867-6205G>A

Variant summary

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

The ENST00000563290.6(SCAPER):​c.1867-6205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 152,174 control chromosomes in the GnomAD database, including 326 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 0.044 (326 hom., cov: 32)
• Consequence: SCAPER ENST00000563290.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25
• Publications: 1 publications found

Genes affected

SCAPER (HGNC:13081): (S-phase cyclin A associated protein in the ER) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

SCAPER Gene-Disease associations (from GenCC):

• intellectual developmental disorder and retinitis pigmentosa; IDDRP

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000563290.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAPER	NM_020843.4	MANE Select	c.1867-6205G>A		intron	N/A	NP_065894.2
	SCAPER	NM_001353009.2		c.1885-6205G>A		intron	N/A	NP_001339938.1
	SCAPER	NM_001353011.2		c.1483-6205G>A		intron	N/A	NP_001339940.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAPER	ENST00000563290.6	TSL:5 MANE Select	c.1867-6205G>A		intron	N/A	ENSP00000454973.1
	SCAPER	ENST00000324767.11	TSL:1	c.1867-6205G>A		intron	N/A	ENSP00000326924.7
	SCAPER	ENST00000538941.6	TSL:1	c.1129-6205G>A		intron	N/A	ENSP00000442190.2

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6722 AN: 152056 Hom.: 324 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.00808

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00478

Gnomad FIN AF: 0.00434

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0354

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

GnomAD4 genome AF: 0.0442 AC: 6731 AN: 152174 Hom.: 326 Cov.: 32 AF XY: 0.0432 AC XY: 3214 AN XY: 74412

African (AFR) AF: 0.124 AC: 5147 AN: 41496

American (AMR) AF: 0.0205 AC: 313 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00808 AC: 28 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00457 AC: 22 AN: 4812

European-Finnish (FIN) AF: 0.00434 AC: 46 AN: 10590

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0162 AC: 1099 AN: 68010

Other (OTH) AF: 0.0351 AC: 74 AN: 2110

Alfa AF: 0.0371 Hom.: 34

Bravo AF: 0.0483

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.76
PhyloP100		-3.2
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: rs280026; hg19: chr15-77031930;