Variant chr1-203486710-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_002725.4(PRELP):c.978C>A(p.Ile326=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,609,040 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0091 ( 29 hom., cov: 33)

Exomes 𝑓: 0.00094 ( 30 hom. )

Consequence

PRELP
NM_002725.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.31

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 1-203486710-C-A is Benign according to our data. Variant chr1-203486710-C-A is described in ClinVar as [Benign]. Clinvar id is 709588.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.31 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00913 (1390/152310) while in subpopulation AFR AF= 0.0316 (1315/41564). AF 95% confidence interval is 0.0302. There are 29 homozygotes in gnomad4. There are 658 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1390 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRELP	NM_002725.4 linkuse as main transcript	c.978C>A	p.Ile326=	synonymous_variant	3/3	ENST00000343110.3
PRELP	NM_201348.2 linkuse as main transcript	c.978C>A	p.Ile326=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRELP	ENST00000343110.3 linkuse as main transcript	c.978C>A	p.Ile326=	synonymous_variant	3/3	1	NM_002725.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00912

AC:

1388

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00239

AC:

599

AN:

250366

Hom.:

AF XY:

0.00167

AC XY:

226

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.0323

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000974

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000938

AC:

1367

AN:

1456730

Hom.:

Cov.:

AF XY:

0.000822

AC XY:

595

AN XY:

723650

show subpopulations

Gnomad4 AFR exome

AF:

0.0327

Gnomad4 AMR exome

AF:

0.00144

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000560

Gnomad4 OTH exome

AF:

0.00208

GnomAD4 genome

AF:

0.00913

AC:

1390

AN:

152310

Hom.:

Cov.:

AF XY:

0.00883

AC XY:

658

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0316

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00399

Hom.:

Bravo

AF:

0.0108

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

6.1

DANN

Benign

0.72

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