rs116581811

Variant names:

• chr6-105278237-G-A
• rs116581811
• NM_002726.5:c.2040C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-105278237-G-A
• chr6-105278237-G-C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002726.5(PREP):​c.2040C>T​(p.His680His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,614,208 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (11 hom.)
• Consequence: PREP NM_002726.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 6-105278237-G-A is Benign according to our data. Variant chr6-105278237-G-A is described in ClinVar as Benign. ClinVar VariationId is 784094.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.034 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0056 (853/152324) while in subpopulation AFR AF = 0.0202 (838/41570). AF 95% confidence interval is 0.019. There are 11 homozygotes in GnomAd4. There are 409 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PREP	NM_002726.5	MANE Select	c.2040C>T	p.His680His	synonymous	Exon 15 of 15	NP_002717.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PREP	ENST00000652536.2	MANE Select	c.2040C>T	p.His680His	synonymous	Exon 15 of 15	ENSP00000499089.1	P48147
	PREP	ENST00000369110.8	TSL:1	c.1842C>T	p.His614His	synonymous	Exon 17 of 17	ENSP00000358106.4	A0A499FJL1
	PREP	ENST00000969640.1		c.2106C>T	p.His702His	synonymous	Exon 16 of 16	ENSP00000639699.1

Frequencies

GnomAD3 genomes AF: 0.00562 AC: 855 AN: 152206 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00150 AC: 377 AN: 251396 AF XY: 0.000986

Gnomad AFR exome AF: 0.0212

Gnomad AMR exome AF: 0.000810

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000585 AC: 855 AN: 1461884 Hom.: 11 Cov.: 31 AF XY: 0.000554 AC XY: 403 AN XY: 727240

African (AFR) AF: 0.0208 AC: 695 AN: 33480

American (AMR) AF: 0.00103 AC: 46 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5762

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1112010

Other (OTH) AF: 0.00109 AC: 66 AN: 60394

GnomAD4 genome AF: 0.00560 AC: 853 AN: 152324 Hom.: 11 Cov.: 32 AF XY: 0.00549 AC XY: 409 AN XY: 74488

African (AFR) AF: 0.0202 AC: 838 AN: 41570

American (AMR) AF: 0.000784 AC: 12 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00338 Hom.: 1

Bravo AF: 0.00664

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.8
DANN	Benign	0.87
PhyloP100		-0.034
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism

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: rs116581811; hg19: chr6-105726112; COSMIC: COSV100964097; COSMIC: COSV100964097;