chr15-76407514-T-C

Variant names:

• chr15-76407514-T-C
• rs8030411
• NM_020843.4:c.3312-2835A>G

Variant summary

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

The NM_020843.4(SCAPER):​c.3312-2835A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,090 control chromosomes in the GnomAD database, including 14,265 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 0.40 (14265 hom., cov: 32)
• Consequence: SCAPER NM_020843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAPER	NM_020843.4	c.3312-2835A>G		intron_variant	Intron 26 of 31	ENST00000563290.6	NP_065894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAPER	ENST00000563290.6	c.3312-2835A>G		intron_variant	Intron 26 of 31	5	NM_020843.4	ENSP00000454973.1
SCAPER	ENST00000324767.11	c.3312-2835A>G		intron_variant	Intron 25 of 30	1		ENSP00000326924.7
SCAPER	ENST00000538941.6	c.2574-2835A>G		intron_variant	Intron 26 of 31	1		ENSP00000442190.2
SCAPER	ENST00000303521.10	n.3376-2835A>G		intron_variant	Intron 25 of 26	2

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60399 AN: 151972 Hom.: 14272 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.397 AC: 60383 AN: 152090 Hom.: 14265 Cov.: 32 AF XY: 0.395 AC XY: 29402 AN XY: 74344

African (AFR) AF: 0.129 AC: 5376 AN: 41518

American (AMR) AF: 0.503 AC: 7679 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1600 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1498 AN: 5168

South Asian (SAS) AF: 0.344 AC: 1662 AN: 4830

European-Finnish (FIN) AF: 0.508 AC: 5366 AN: 10568

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.525 AC: 35651 AN: 67960

Other (OTH) AF: 0.429 AC: 906 AN: 2114

Alfa AF: 0.439 Hom.: 3132

Bravo AF: 0.389

Asia WGS AF: 0.290 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.7
DANN	Benign	0.70
PhyloP100		1.4
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: rs8030411; hg19: chr15-76699855;