dbSNP rs2294910: PREX1:c.1881+76T>C (chr20-48659843-A-G) – 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.1881+76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,595,758 control chromosomes in the GnomAD database, including 31,108 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 0.18 ( 2457 hom., cov: 31)

Exomes 𝑓: 0.20 ( 28651 hom. )

Consequence

PREX1
NM_020820.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0470

Publications

7 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:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PREX1	NM_020820.4 link	c.1881+76T>C		intron_variant	Intron 16 of 39	ENST00000371941.4	NP_065871.3	Q8TCU6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4 link	c.1881+76T>C		intron_variant	Intron 16 of 39	1	NM_020820.4	ENSP00000361009.3		Q8TCU6-1

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26642

AN:

152010

Hom.:

2453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.212

GnomAD4 exome

AF:

0.196

AC:

283022

AN:

1443630

Hom.:

28651

AF XY:

0.199

AC XY:

142639

AN XY:

717610

show subpopulations

African (AFR)

AF:

0.106

AC:

3521

AN:

33116

American (AMR)

AF:

0.249

AC:

11000

AN:

44220

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

6115

AN:

25828

East Asian (EAS)

AF:

0.136

AC:

5377

AN:

39470

South Asian (SAS)

AF:

0.265

AC:

22637

AN:

85352

European-Finnish (FIN)

AF:

0.157

AC:

8212

AN:

52140

Middle Eastern (MID)

AF:

0.269

AC:

1168

AN:

4344

European-Non Finnish (NFE)

AF:

0.194

AC:

213149

AN:

1099520

Other (OTH)

AF:

0.199

AC:

11843

AN:

59640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

11765

23530

35296

47061

58826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7536

15072

22608

30144

37680

<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:

0.175

AC:

26666

AN:

152128

Hom.:

2457

Cov.:

AF XY:

0.175

AC XY:

13034

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.111

AC:

4601

AN:

41504

American (AMR)

AF:

0.231

AC:

3537

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

820

AN:

3470

East Asian (EAS)

AF:

0.146

AC:

755

AN:

5166

South Asian (SAS)

AF:

0.276

AC:

1333

AN:

4822

European-Finnish (FIN)

AF:

0.166

AC:

1753

AN:

10588

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.193

AC:

13137

AN:

67972

Other (OTH)

AF:

0.214

AC:

450

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1139

2279

3418

4558

5697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.192

Hom.:

9286

Bravo

AF:

0.173

Asia WGS

AF:

0.220

AC:

764

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.48

PhyloP100

0.047

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