rs6914611

Variant names:

• chr6-105374290-T-C
• rs6914611
• NM_002726.5:c.386-712A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.81).
• 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 rank	MANE	Protein	UniProt
PREP	NM_002726.5	c.386-712A>G		intron_variant	Intron 4 of 14	ENST00000652536.2	NP_002717.3
PREP	XM_011535925.4	c.386-712A>G		intron_variant	Intron 4 of 10		XP_011534227.1
PREP	XM_005267044.4	c.386-712A>G		intron_variant	Intron 4 of 10		XP_005267101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PREP	ENST00000652536.2	c.386-712A>G		intron_variant	Intron 4 of 14		NM_002726.5	ENSP00000499089.1
PREP	ENST00000369110.8	c.188-712A>G		intron_variant	Intron 6 of 16	1		ENSP00000358106.4

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

African (AFR) AF: 0.133 AC: 5540 AN: 41510

American (AMR) AF: 0.104 AC: 1585 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3472

East Asian (EAS) AF: 0.00348 AC: 18 AN: 5178

South Asian (SAS) AF: 0.0638 AC: 308 AN: 4828

European-Finnish (FIN) AF: 0.0661 AC: 700 AN: 10596

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7714 AN: 68010

Other (OTH) AF: 0.129 AC: 273 AN: 2110

Alfa AF: 0.115 Hom.: 879

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
PhyloP100		0.40
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: rs6914611; hg19: chr6-105822165; COSMIC: COSV64871828;