chr20-48636586-G-A
Position:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_020820.4(PREX1):c.4044C>T(p.Tyr1348=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 1,611,812 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0038 ( 4 hom., cov: 34)
Exomes 𝑓: 0.0051 ( 33 hom. )
Consequence
PREX1
NM_020820.4 synonymous
NM_020820.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.931
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 20-48636586-G-A is Benign according to our data. Variant chr20-48636586-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 774531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.931 with no splicing effect.
BS2
High AC in GnomAd4 at 577 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PREX1 | NM_020820.4 | c.4044C>T | p.Tyr1348= | synonymous_variant | 32/40 | ENST00000371941.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PREX1 | ENST00000371941.4 | c.4044C>T | p.Tyr1348= | synonymous_variant | 32/40 | 1 | NM_020820.4 | P1 | |
PREX1 | ENST00000482556.5 | c.2010C>T | p.Tyr670= | synonymous_variant, NMD_transcript_variant | 15/22 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00379 AC: 577AN: 152264Hom.: 4 Cov.: 34
GnomAD3 genomes
AF:
AC:
577
AN:
152264
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00374 AC: 897AN: 239826Hom.: 6 AF XY: 0.00370 AC XY: 487AN XY: 131720
GnomAD3 exomes
AF:
AC:
897
AN:
239826
Hom.:
AF XY:
AC XY:
487
AN XY:
131720
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00514 AC: 7499AN: 1459430Hom.: 33 Cov.: 32 AF XY: 0.00497 AC XY: 3610AN XY: 726124
GnomAD4 exome
AF:
AC:
7499
AN:
1459430
Hom.:
Cov.:
32
AF XY:
AC XY:
3610
AN XY:
726124
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00379 AC: 577AN: 152382Hom.: 4 Cov.: 34 AF XY: 0.00353 AC XY: 263AN XY: 74514
GnomAD4 genome
AF:
AC:
577
AN:
152382
Hom.:
Cov.:
34
AF XY:
AC XY:
263
AN XY:
74514
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
5
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | PREX1: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 26, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at