Genetic Variant PLRG1:c.940-262G>C (chr4-154540315-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002669.4(PLRG1):c.940-262G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000236 in 422,932 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000024 ( 0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLRG1	NM_002669.4 link	c.940-262G>C		intron_variant	Intron 10 of 14	ENST00000499023.7	NP_002660.1
PLRG1	NM_001201564.2 link	c.913-262G>C		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>C	intron_variant	Intron 10 of 14	1	NM_002669.4	ENSP00000424417.1
PLRG1	ENST00000302078.9 link	c.913-262G>C	intron_variant	Intron 10 of 14	1		ENSP00000303191.5
PLRG1	ENST00000506627.5 link	n.253-262G>C	intron_variant	Intron 2 of 6	5		ENSP00000425914.1
PLRG1	ENST00000507125.1 link	n.-43G>C	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000236

AC:

AN:

422932

Hom.:

Cov.:

AF XY:

0.00000450

AC XY:

AN XY:

222370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11908

American (AMR)

AF:

0.00

AC:

AN:

15088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13270

East Asian (EAS)

AF:

0.00

AC:

AN:

30222

South Asian (SAS)

AF:

0.00

AC:

AN:

38326

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1896

European-Non Finnish (NFE)

AF:

0.00000387

AC:

AN:

258404

Other (OTH)

AF:

0.00

AC:

AN:

24860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.64

(source)

DANN

Benign

0.61

PhyloP100

-3.5

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over