Genetic Variant NM_020820.4:c.520-131C>A (chr20-48726522-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020820.4(PREX1):c.520-131C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 658,532 control chromosomes in the GnomAD database, including 9,422 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 0.14 ( 1835 hom., cov: 33)

Exomes 𝑓: 0.16 ( 7587 hom. )

Consequence

PREX1
NM_020820.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.06

Publications

21 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PREX1	NM_020820.4 link	c.520-131C>A	intron_variant	Intron 4 of 39	ENST00000371941.4	NP_065871.3	Q8TCU6-1
PREX1	XM_047440331.1 link	c.-6-131C>A	intron_variant	Intron 5 of 40		XP_047296287.1
PREX1	XM_047440332.1 link	c.-6-131C>A	intron_variant	Intron 4 of 39		XP_047296288.1
PREX1	XM_047440333.1 link	c.-6-131C>A	intron_variant	Intron 5 of 40		XP_047296289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4 link	c.520-131C>A		intron_variant	Intron 4 of 39	1	NM_020820.4	ENSP00000361009.3		Q8TCU6-1

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22024

AN:

152090

Hom.:

1831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.0959

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.178

GnomAD4 exome

AF:

0.164

AC:

82827

AN:

506324

Hom.:

7587

AF XY:

0.168

AC XY:

44507

AN XY:

265278

show subpopulations

African (AFR)

AF:

0.104

AC:

1447

AN:

13864

American (AMR)

AF:

0.281

AC:

6808

AN:

24262

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

2638

AN:

15400

East Asian (EAS)

AF:

0.229

AC:

7024

AN:

30718

South Asian (SAS)

AF:

0.243

AC:

12196

AN:

50274

European-Finnish (FIN)

AF:

0.0950

AC:

3852

AN:

40554

Middle Eastern (MID)

AF:

0.207

AC:

450

AN:

2170

European-Non Finnish (NFE)

AF:

0.146

AC:

43887

AN:

301534

Other (OTH)

AF:

0.164

AC:

4525

AN:

27548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

3151

6302

9454

12605

15756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

540

1080

1620

2160

2700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.145

AC:

22049

AN:

152208

Hom.:

1835

Cov.:

AF XY:

0.147

AC XY:

10937

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.101

AC:

4213

AN:

41552

American (AMR)

AF:

0.246

AC:

3752

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

559

AN:

3464

East Asian (EAS)

AF:

0.185

AC:

957

AN:

5178

South Asian (SAS)

AF:

0.262

AC:

1260

AN:

4812

European-Finnish (FIN)

AF:

0.0959

AC:

1017

AN:

10606

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.143

AC:

9722

AN:

68002

Other (OTH)

AF:

0.180

AC:

379

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

931

1862

2793

3724

4655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.151

Hom.:

5735

Bravo

AF:

0.151

Asia WGS

AF:

0.230

AC:

798

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.1

(source)

DANN

Benign

0.57

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over