15-76404427-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020843.4(SCAPER):c.3467+97A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 1,209,514 control chromosomes in the GnomAD database, including 3,055 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 0.078 (525 hom., cov: 31)
  • Exomes 𝑓: 0.065 (2530 hom.)
• Consequence: SCAPER NM_020843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCAPER	NM_020843.4	c.3467+97A>G		intron_variant		ENST00000563290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAPER	ENST00000563290.6	c.3467+97A>G		intron_variant		5	NM_020843.4	P1
SCAPER	ENST00000324767.11	c.3467+97A>G		intron_variant		1		P1
SCAPER	ENST00000538941.6	c.2729+97A>G		intron_variant		1
SCAPER	ENST00000303521.10	n.3531+97A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11821 AN: 152112 Hom.: 525 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0726

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0351

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.0616

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0775

GnomAD4 exome AF: 0.0651 AC: 68817 AN: 1057284 Hom.: 2530 AF XY: 0.0653 AC XY: 34122 AN XY: 522250

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.0444

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.0241

Gnomad4 SAS exome AF: 0.0550

Gnomad4 FIN exome AF: 0.0560

Gnomad4 NFE exome AF: 0.0656

Gnomad4 OTH exome AF: 0.0716

GnomAD4 genome AF: 0.0777 AC: 11830 AN: 152230 Hom.: 525 Cov.: 31 AF XY: 0.0782 AC XY: 5820 AN XY: 74442

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0725

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0352

Gnomad4 SAS AF: 0.0574

Gnomad4 FIN AF: 0.0616

Gnomad4 NFE AF: 0.0671

Gnomad4 OTH AF: 0.0772

Alfa AF: 0.0717 Hom.: 582

Bravo AF: 0.0794

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.79
Dann	Benign	0.88

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

LitVar

Other links and lift over

dbSNP: rs3743175; hg19: chr15-76696768; COSMIC: COSV57739279;