Variant 1-203483868-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002725.4(PRELP):c.684G>A(p.Leu228=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,614,164 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 18 hom. )

Consequence

PRELP
NM_002725.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.423

Variant links:

Genes affected

PRELP (HGNC:9357): (proline and arginine rich end leucine rich repeat protein) The protein encoded by this gene is a leucine-rich repeat protein present in connective tissue extracellular matrix. This protein functions as a molecule anchoring basement membranes to the underlying connective tissue. This protein has been shown to bind type I collagen to basement membranes and type II collagen to cartilage. It also binds the basement membrane heparan sulfate proteoglycan perlecan. This protein is suggested to be involved in the pathogenesis of Hutchinson-Gilford progeria (HGP), which is reported to lack the binding of collagen in basement membranes and cartilage. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

PRELP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 1-203483868-G-A is Benign according to our data. Variant chr1-203483868-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639817.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.423 with no splicing effect.

BS2

High AC in GnomAd4 at 531 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRELP	NM_002725.4 linkuse as main transcript	c.684G>A	p.Leu228=	synonymous_variant	2/3	ENST00000343110.3
PRELP	NM_201348.2 linkuse as main transcript	c.684G>A	p.Leu228=	synonymous_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRELP	ENST00000343110.3 linkuse as main transcript	c.684G>A	p.Leu228=	synonymous_variant	2/3	1	NM_002725.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

532

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00539

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00377

AC:

949

AN:

251474

Hom.:

AF XY:

0.00391

AC XY:

531

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00405

Gnomad FIN exome

AF:

0.00254

Gnomad NFE exome

AF:

0.00535

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00489

AC:

7146

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00487

AC XY:

3540

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00474

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00439

Gnomad4 FIN exome

AF:

0.00288

Gnomad4 NFE exome

AF:

0.00546

Gnomad4 OTH exome

AF:

0.00452

GnomAD4 genome

AF:

0.00349

AC:

531

AN:

152272

Hom.:

Cov.:

AF XY:

0.00343

AC XY:

255

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00540

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00485

Hom.:

Bravo

AF:

0.00335

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00502

EpiControl

AF:

0.00445

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

PRELP: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.7

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over