rs6914611

chr6-105374290-T-C

Variant summary

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

The NM_002726.5(PREP):c.386-712A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,200 control chromosomes in the GnomAD database, including 972 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 0.11 (972 hom., cov: 32)
• Consequence: PREP NM_002726.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PREP	NM_002726.5	c.386-712A>G		intron_variant		ENST00000652536.2
PREP	XM_005267044.4	c.386-712A>G		intron_variant
PREP	XM_011535925.4	c.386-712A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PREP	ENST00000652536.2	c.386-712A>G		intron_variant			NM_002726.5	P1
PREP	ENST00000369110.8	c.188-712A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16694 AN: 152082 Hom.: 969 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.0661

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.110 AC: 16709 AN: 152200 Hom.: 972 Cov.: 32 AF XY: 0.106 AC XY: 7897 AN XY: 74426

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.00348

Gnomad4 SAS AF: 0.0638

Gnomad4 FIN AF: 0.0661

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.129

Alfa AF: 0.112 Hom.: 524

Bravo AF: 0.114

Asia WGS AF: 0.0410 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.2
Dann	Benign	0.59

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: rs6914611; hg19: chr6-105822165; COSMIC: COSV64871828;