Genetic Variant PLRG1:c.1043-94A>G (chr4-154539307-T-C) – 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.1043-94A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 774,648 control chromosomes in the GnomAD database, including 25,026 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 0.21 ( 3795 hom., cov: 33)

Exomes 𝑓: 0.24 ( 21231 hom. )

Consequence

PLRG1
NM_002669.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002669.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLRG1	NM_002669.4	MANE Select	c.1043-94A>G		intron	N/A	NP_002660.1
	PLRG1	NM_001201564.2		c.1016-94A>G		intron	N/A	NP_001188493.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PLRG1	ENST00000499023.7	TSL:1 MANE Select	c.1043-94A>G	intron	N/A	ENSP00000424417.1
PLRG1	ENST00000302078.9	TSL:1	c.1016-94A>G	intron	N/A	ENSP00000303191.5
PLRG1	ENST00000506627.5	TSL:5	n.356-94A>G	intron	N/A	ENSP00000425914.1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31272

AN:

151972

Hom.:

3795

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.203

GnomAD4 exome

AF:

0.243

AC:

151287

AN:

622558

Hom.:

21231

AF XY:

0.244

AC XY:

80713

AN XY:

331286

show subpopulations

African (AFR)

AF:

0.122

AC:

2027

AN:

16664

American (AMR)

AF:

0.256

AC:

8628

AN:

33740

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

3200

AN:

17530

East Asian (EAS)

AF:

0.599

AC:

21053

AN:

35132

South Asian (SAS)

AF:

0.282

AC:

16016

AN:

56812

European-Finnish (FIN)

AF:

0.274

AC:

12158

AN:

44414

Middle Eastern (MID)

AF:

0.180

AC:

480

AN:

2662

European-Non Finnish (NFE)

AF:

0.210

AC:

80649

AN:

383808

Other (OTH)

AF:

0.223

AC:

7076

AN:

31796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

5272

10544

15817

21089

26361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1318

2636

3954

5272

6590

<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:

0.206

AC:

31289

AN:

152090

Hom.:

3795

Cov.:

AF XY:

0.212

AC XY:

15750

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.124

AC:

5134

AN:

41538

American (AMR)

AF:

0.225

AC:

3439

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

592

AN:

3470

East Asian (EAS)

AF:

0.551

AC:

2854

AN:

5180

South Asian (SAS)

AF:

0.261

AC:

1256

AN:

4818

European-Finnish (FIN)

AF:

0.262

AC:

2764

AN:

10568

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.213

AC:

14464

AN:

67932

Other (OTH)

AF:

0.202

AC:

427

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1252

2505

3757

5010

6262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.196

Hom.:

3240

Bravo

AF:

0.201

Asia WGS

AF:

0.352

AC:

1220

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

(source)

DANN

Benign

0.53

PhyloP100

-1.0

PromoterAI

0.037

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over