rs7654425

Variant summary

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

The NM_002669.4(PLRG1):​c.*1229T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 150,792 control chromosomes in the GnomAD database, including 5,754 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 0.26 ( 5754 hom., cov: 29)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PLRG1
NM_002669.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13
Variant links:
Genes affected
PLRG1 (HGNC:9089): (pleiotropic regulator 1) This gene encodes a core component of the cell division cycle 5-like (CDC5L) complex. The CDC5L complex is part of the spliceosome and is required for pre-mRNA splicing. The encoded protein plays a critical role in alternative splice site selection. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

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=-0.91).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLRG1NM_002669.4 linkc.*1229T>C 3_prime_UTR_variant Exon 15 of 15 ENST00000499023.7 NP_002660.1 O43660-1
PLRG1NM_001201564.2 linkc.*1229T>C 3_prime_UTR_variant Exon 15 of 15 NP_001188493.1 O43660-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLRG1ENST00000499023 linkc.*1229T>C 3_prime_UTR_variant Exon 15 of 15 1 NM_002669.4 ENSP00000424417.1 O43660-1

Frequencies

GnomAD3 genomes
AF:
0.265
AC:
39937
AN:
150674
Hom.:
5756
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.178
Gnomad AMI
AF:
0.157
Gnomad AMR
AF:
0.227
Gnomad ASJ
AF:
0.329
Gnomad EAS
AF:
0.140
Gnomad SAS
AF:
0.338
Gnomad FIN
AF:
0.240
Gnomad MID
AF:
0.364
Gnomad NFE
AF:
0.332
Gnomad OTH
AF:
0.297
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
2
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
Gnomad4 AFR exome
AC:
0
AN:
0
Gnomad4 AMR exome
AC:
0
AN:
0
Gnomad4 ASJ exome
AC:
0
AN:
0
Gnomad4 EAS exome
AC:
0
AN:
0
Gnomad4 SAS exome
AC:
0
AN:
0
Gnomad4 FIN exome
AC:
0
AN:
0
Gnomad4 NFE exome
AF:
0.00
AC:
0
AN:
2
Gnomad4 Remaining exome
AC:
0
AN:
0
GnomAD4 genome
AF:
0.265
AC:
39924
AN:
150792
Hom.:
5754
Cov.:
29
AF XY:
0.261
AC XY:
19171
AN XY:
73564
show subpopulations
Gnomad4 AFR
AF:
0.177
AC:
0.177438
AN:
0.177438
Gnomad4 AMR
AF:
0.227
AC:
0.226777
AN:
0.226777
Gnomad4 ASJ
AF:
0.329
AC:
0.328787
AN:
0.328787
Gnomad4 EAS
AF:
0.139
AC:
0.139386
AN:
0.139386
Gnomad4 SAS
AF:
0.336
AC:
0.335938
AN:
0.335938
Gnomad4 FIN
AF:
0.240
AC:
0.239535
AN:
0.239535
Gnomad4 NFE
AF:
0.331
AC:
0.331491
AN:
0.331491
Gnomad4 OTH
AF:
0.293
AC:
0.293301
AN:
0.293301
Heterozygous variant carriers
0
1396
2793
4189
5586
6982
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
418
836
1254
1672
2090
<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:
0.308
Hom.:
9718
Bravo
AF:
0.259
Asia WGS
AF:
0.260
AC:
903
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.66
DANN
Benign
0.32
Mutation Taster
=100/0
polymorphism (auto)

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.

Other links and lift over

dbSNP: rs7654425; hg19: chr4-155456608; API