Genetic Variant NM_002669.4: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLRG1	NM_002669.4 link	c.1043-94A>G		intron_variant	Intron 11 of 14	ENST00000499023.7	NP_002660.1
PLRG1	NM_001201564.2 link	c.1016-94A>G		intron_variant	Intron 11 of 14		NP_001188493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLRG1	ENST00000499023.7 link	c.1043-94A>G		intron_variant	Intron 11 of 14	1	NM_002669.4	ENSP00000424417.1

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 v4.3

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

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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