NM_002726.5:c.1317+134C>T

Variant names:

• chr6-105323531-G-A
• rs12213914
• NM_002726.5:c.1317+134C>T

Variant summary

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

The NM_002726.5(PREP):​c.1317+134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 798,840 control chromosomes in the GnomAD database, including 2,684 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 0.059 (363 hom., cov: 32)
  • Exomes 𝑓: 0.077 (2321 hom.)
• Consequence: PREP NM_002726.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002726.5. 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
	PREP	NM_002726.5	MANE Select	c.1317+134C>T		intron	N/A	NP_002717.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PREP	ENST00000652536.2	MANE Select	c.1317+134C>T		intron	N/A	ENSP00000499089.1
	PREP	ENST00000369110.8	TSL:1	c.1119+134C>T		intron	N/A	ENSP00000358106.4
	PREP	ENST00000448705.1	TSL:2	c.102+134C>T		intron	N/A	ENSP00000401796.1

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 9039 AN: 152060 Hom.: 364 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.00735

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0656

GnomAD4 exome AF: 0.0771 AC: 49831 AN: 646664 Hom.: 2321 AF XY: 0.0806 AC XY: 27247 AN XY: 338030

African (AFR) AF: 0.0171 AC: 290 AN: 16956

American (AMR) AF: 0.0413 AC: 1260 AN: 30540

Ashkenazi Jewish (ASJ) AF: 0.0779 AC: 1313 AN: 16858

East Asian (EAS) AF: 0.00208 AC: 67 AN: 32234

South Asian (SAS) AF: 0.136 AC: 7608 AN: 55796

European-Finnish (FIN) AF: 0.114 AC: 3972 AN: 34822

Middle Eastern (MID) AF: 0.109 AC: 439 AN: 4010

European-Non Finnish (NFE) AF: 0.0766 AC: 32363 AN: 422506

Other (OTH) AF: 0.0765 AC: 2519 AN: 32942

GnomAD4 genome AF: 0.0594 AC: 9032 AN: 152176 Hom.: 363 Cov.: 32 AF XY: 0.0615 AC XY: 4573 AN XY: 74366

African (AFR) AF: 0.0174 AC: 724 AN: 41534

American (AMR) AF: 0.0508 AC: 777 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3470

East Asian (EAS) AF: 0.00756 AC: 39 AN: 5158

South Asian (SAS) AF: 0.133 AC: 641 AN: 4826

European-Finnish (FIN) AF: 0.108 AC: 1143 AN: 10572

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0771 AC: 5245 AN: 68010

Other (OTH) AF: 0.0649 AC: 137 AN: 2110

Alfa AF: 0.0627 Hom.: 46

Bravo AF: 0.0508

Asia WGS AF: 0.0610 AC: 211 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.59
PhyloP100		-0.75
PromoterAI		-0.016	Neutral
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: rs12213914; hg19: chr6-105771406;