Variant 20-48629589-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020820.4(PREX1):c.4626C>T(p.Leu1542Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0942 in 1,613,766 control chromosomes in the GnomAD database, including 8,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 626 hom., cov: 32)

Exomes 𝑓: 0.095 ( 7423 hom. )

Consequence

PREX1
NM_020820.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0680

Variant links:

Genes affected

PREX1 (HGNC:32594): (phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1) The protein encoded by this gene acts as a guanine nucleotide exchange factor for the RHO family of small GTP-binding proteins (RACs). It has been shown to bind to and activate RAC1 by exchanging bound GDP for free GTP. The encoded protein, which is found mainly in the cytoplasm, is activated by phosphatidylinositol-3,4,5-trisphosphate and the beta-gamma subunits of heterotrimeric G proteins. [provided by RefSeq, Jul 2008]

PREX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 20-48629589-G-A is Benign according to our data. Variant chr20-48629589-G-A is described in ClinVar as [Benign]. Clinvar id is 1235020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.068 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREX1	NM_020820.4 link	c.4626C>T	p.Leu1542Leu	synonymous_variant	37/40	ENST00000371941.4	NP_065871.3	Q8TCU6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PREX1	ENST00000371941.4 link	c.4626C>T	p.Leu1542Leu	synonymous_variant	37/40	1	NM_020820.4	ENSP00000361009.3	Q8TCU6-1
PREX1	ENST00000482556.5 link	n.*44C>T		non_coding_transcript_exon_variant	19/22	2		ENSP00000434632.1	H0YDZ4
PREX1	ENST00000482556.5 link	n.*44C>T		3_prime_UTR_variant	19/22	2		ENSP00000434632.1	H0YDZ4

Frequencies

GnomAD3 genomes

AF:

0.0849

AC:

12911

AN:

152152

Hom.:

627

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0470

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.0662

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0894

Gnomad OTH

AF:

0.0951

GnomAD3 exomes

AF:

0.105

AC:

26396

AN:

251238

Hom.:

1600

AF XY:

0.107

AC XY:

14560

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.0472

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.0681

Gnomad NFE exome

AF:

0.0913

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.0952

AC:

139118

AN:

1461496

Hom.:

7423

Cov.:

AF XY:

0.0969

AC XY:

70453

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.0481

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.175

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.0726

Gnomad4 NFE exome

AF:

0.0882

Gnomad4 OTH exome

AF:

0.0998

GnomAD4 genome

AF:

0.0849

AC:

12922

AN:

152270

Hom.:

626

Cov.:

AF XY:

0.0859

AC XY:

6398

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0471

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.152

Gnomad4 FIN

AF:

0.0662

Gnomad4 NFE

AF:

0.0894

Gnomad4 OTH

AF:

0.0937

Alfa

AF:

0.0938

Hom.:

987

Bravo

AF:

0.0868

Asia WGS

AF:

0.124

AC:

432

AN:

3476

EpiCase

AF:

0.0937

EpiControl

AF:

0.0959

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.3

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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