4-154540315-C-T

Position:

• chr4-154540315-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PLRG1	NM_002669.4	c.940-262G>A		intron_variant		ENST00000499023.7
PLRG1	NM_001201564.2	c.913-262G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLRG1	ENST00000499023.7	c.940-262G>A		intron_variant		1	NM_002669.4	P1
PLRG1	ENST00000302078.9	c.913-262G>A		intron_variant		1
PLRG1	ENST00000506627.5	c.255-262G>A		intron_variant, NMD_transcript_variant		5
PLRG1	ENST00000507125.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131622 AN: 151990 Hom.: 57107 Cov.: 32

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.: 2 AF XY: 0.867 AC XY: 192711 AN XY: 222208

Gnomad4 AFR exome AF: 0.872

Gnomad4 AMR exome AF: 0.858

Gnomad4 ASJ exome AF: 0.783

Gnomad4 EAS exome AF: 0.984

Gnomad4 SAS exome AF: 0.879

Gnomad4 FIN exome AF: 0.816

Gnomad4 NFE exome AF: 0.863

Gnomad4 OTH exome AF: 0.863

GnomAD4 genome AF: 0.866 AC: 131729 AN: 152108 Hom.: 57156 Cov.: 32 AF XY: 0.866 AC XY: 64385 AN XY: 74346

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.871

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.879

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.876

Alfa AF: 0.863 Hom.: 30395

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
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs7698829; hg19: chr4-155461467;