Variant 15-76381375-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_020843.4(SCAPER):c.3705+3A>G variant causes a splice donor region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,607,546 control chromosomes in the GnomAD database, including 99,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8537 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90644 hom. )

Consequence

SCAPER
NM_020843.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.9662

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.36

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 15-76381375-T-C is Benign according to our data. Variant chr15-76381375-T-C is described in ClinVar as [Benign]. Clinvar id is 1327980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-76381375-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCAPER	NM_020843.4 linkuse as main transcript	c.3705+3A>G		splice_donor_region_variant, intron_variant		ENST00000563290.6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAPER	ENST00000563290.6 linkuse as main transcript	c.3705+3A>G	splice_donor_region_variant, intron_variant		5	NM_020843.4	P1	Q9BY12-1
SCAPER	ENST00000324767.11 linkuse as main transcript	c.3705+3A>G	splice_donor_region_variant, intron_variant		1		P1	Q9BY12-1
SCAPER	ENST00000538941.6 linkuse as main transcript	c.2967+3A>G	splice_donor_region_variant, intron_variant		1			Q9BY12-3
SCAPER	ENST00000303521.10 linkuse as main transcript	n.3772A>G	non_coding_transcript_exon_variant	27/27	2

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49781

AN:

152006

Hom.:

8526

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.580

Gnomad SAS

AF:

0.529

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.331

GnomAD3 exomes

AF:

0.371

AC:

89798

AN:

242194

Hom.:

17564

AF XY:

0.377

AC XY:

49391

AN XY:

131118

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.565

Gnomad SAS exome

AF:

0.526

Gnomad FIN exome

AF:

0.326

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.350

GnomAD4 exome

AF:

0.346

AC:

504060

AN:

1455422

Hom.:

90644

Cov.:

AF XY:

0.351

AC XY:

254190

AN XY:

723632

show subpopulations

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.365

Gnomad4 ASJ exome

AF:

0.356

Gnomad4 EAS exome

AF:

0.581

Gnomad4 SAS exome

AF:

0.519

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.326

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.328

AC:

49824

AN:

152124

Hom.:

8537

Cov.:

AF XY:

0.331

AC XY:

24577

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.269

Gnomad4 AMR

AF:

0.330

Gnomad4 ASJ

AF:

0.349

Gnomad4 EAS

AF:

0.581

Gnomad4 SAS

AF:

0.529

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.329

Hom.:

20088

Bravo

AF:

0.322

Asia WGS

AF:

0.538

AC:

1869

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Intellectual developmental disorder and retinitis pigmentosa; IDDRP

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

SCAPER-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Benign

0.63

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.24

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over