Genetic Variant PLRG1:c.940-262G>A (chr4-154540315-C-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_002669.4(PLRG1):c.940-262G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 574,746 control chromosomes in the GnomAD database, including 216,535 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 0.87 ( 57156 hom., cov: 32)

Exomes 𝑓: 0.87 ( 159379 hom. )

Consequence

PLRG1
NM_002669.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.49

Publications

3 publications found

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]

PLRG1 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLRG1	NM_002669.4 link	c.940-262G>A		intron_variant	Intron 10 of 14	ENST00000499023.7	NP_002660.1
PLRG1	NM_001201564.2 link	c.913-262G>A		intron_variant	Intron 10 of 14		NP_001188493.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PLRG1	ENST00000499023.7 link	c.940-262G>A	intron_variant	Intron 10 of 14	1	NM_002669.4	ENSP00000424417.1
PLRG1	ENST00000302078.9 link	c.913-262G>A	intron_variant	Intron 10 of 14	1		ENSP00000303191.5
PLRG1	ENST00000506627.5 link	n.253-262G>A	intron_variant	Intron 2 of 6	5		ENSP00000425914.1
PLRG1	ENST00000507125.1 link	n.-43G>A	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.866

AC:

131622

AN:

151990

Hom.:

57107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.873

Gnomad AMI

AF:

0.906

Gnomad AMR

AF:

0.871

Gnomad ASJ

AF:

0.774

Gnomad EAS

AF:

0.965

Gnomad SAS

AF:

0.880

Gnomad FIN

AF:

0.825

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.862

Gnomad OTH

AF:

0.877

GnomAD4 exome

AF:

0.867

AC:

366587

AN:

422638

Hom.:

159379

Cov.:

AF XY:

0.867

AC XY:

192711

AN XY:

222208

show subpopulations

African (AFR)

AF:

0.872

AC:

10379

AN:

11906

American (AMR)

AF:

0.858

AC:

12942

AN:

15076

Ashkenazi Jewish (ASJ)

AF:

0.783

AC:

10374

AN:

13248

East Asian (EAS)

AF:

0.984

AC:

29718

AN:

30216

South Asian (SAS)

AF:

0.879

AC:

33671

AN:

38290

European-Finnish (FIN)

AF:

0.816

AC:

23594

AN:

28916

Middle Eastern (MID)

AF:

0.864

AC:

1639

AN:

1896

European-Non Finnish (NFE)

AF:

0.863

AC:

222835

AN:

258240

Other (OTH)

AF:

0.863

AC:

21435

AN:

24850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2298

4596

6894

9192

11490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.866

AC:

131729

AN:

152108

Hom.:

57156

Cov.:

AF XY:

0.866

AC XY:

64385

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.873

AC:

36246

AN:

41512

American (AMR)

AF:

0.871

AC:

13298

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.774

AC:

2687

AN:

3472

East Asian (EAS)

AF:

0.965

AC:

4999

AN:

5182

South Asian (SAS)

AF:

0.879

AC:

4240

AN:

4822

European-Finnish (FIN)

AF:

0.825

AC:

8734

AN:

10592

Middle Eastern (MID)

AF:

0.873

AC:

255

AN:

292

European-Non Finnish (NFE)

AF:

0.862

AC:

58600

AN:

67958

Other (OTH)

AF:

0.876

AC:

1844

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

916

1832

2748

3664

4580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.864

Hom.:

55765

Bravo

AF:

0.870

Asia WGS

AF:

0.919

AC:

3194

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.82

(source)

DANN

Benign

0.64

PhyloP100

-3.5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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