rs1190053

chr6-105297313-G-A

Variant summary

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

The NM_002726.5(PREP):c.1318-8419C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.091 in 152,120 control chromosomes in the GnomAD database, including 720 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 0.091 (720 hom., cov: 32)
• Consequence: PREP NM_002726.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810

Genes affected

PREP (HGNC:9358): (prolyl endopeptidase) The protein encoded by this gene is a cytosolic prolyl endopeptidase that cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long. Prolyl endopeptidases have been reported to be involved in the maturation and degradation of peptide hormones and neuropeptides. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PREP	NM_002726.5	c.1318-8419C>T		intron_variant		ENST00000652536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PREP	ENST00000652536.2	c.1318-8419C>T		intron_variant			NM_002726.5	P1
PREP	ENST00000369110.8	c.1120-8419C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13824 AN: 152002 Hom.: 722 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0587

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.0878

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0723

Gnomad OTH AF: 0.0849

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

GnomAD4 genome AF: 0.0910 AC: 13842 AN: 152120 Hom.: 720 Cov.: 32 AF XY: 0.0926 AC XY: 6886 AN XY: 74372

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0587

Gnomad4 ASJ AF: 0.0654

Gnomad4 EAS AF: 0.0882

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0723

Gnomad4 OTH AF: 0.0840

Alfa AF: 0.0765 Hom.: 651

Bravo AF: 0.0880

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.078
Dann	Benign	0.42

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: rs1190053; hg19: chr6-105745188;