dbSNP rs12213914: PREP:c.1317+134C>T (chr6-105323531-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.746

Publications

2 publications found

Variant links:

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]

PREP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PREP	NM_002726.5 link	c.1317+134C>T	intron_variant	Intron 10 of 14	ENST00000652536.2	NP_002717.3
PREP	XM_011535925.4 link	c.1317+134C>T	intron_variant	Intron 10 of 10		XP_011534227.1
PREP	XM_005267044.4 link	c.1317+134C>T	intron_variant	Intron 10 of 10		XP_005267101.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PREP	ENST00000652536.2 link	c.1317+134C>T	intron_variant	Intron 10 of 14		NM_002726.5	ENSP00000499089.1
PREP	ENST00000369110.8 link	c.1119+134C>T	intron_variant	Intron 12 of 16	1		ENSP00000358106.4
PREP	ENST00000448705.1 link	c.102+134C>T	intron_variant	Intron 1 of 1	2		ENSP00000401796.1

Frequencies

GnomAD3 genomes

AF:

0.0594

AC:

9039

AN:

152060

Hom.:

364

Cov.:

show subpopulations

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

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2226

4452

6677

8903

11129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

606

1212

1818

2424

3030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0594

AC:

9032

AN:

152176

Hom.:

363

Cov.:

AF XY:

0.0615

AC XY:

4573

AN XY:

74366

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0771

AC:

5245

AN:

68010

Other (OTH)

AF:

0.0649

AC:

137

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

437

874

1311

1748

2185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0627

Hom.:

Bravo

AF:

0.0508

Asia WGS

AF:

0.0610

AC:

211

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.35

(source)

DANN

Benign

0.59

PhyloP100

-0.75

PromoterAI

-0.016

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over