NM_002669.4:c.940-262G>A

Variant names:

• chr4-154540315-C-T
• rs7698829
• NM_002669.4:c.940-262G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

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.

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.940-262G>A		intron	N/A	NP_002660.1
	PLRG1	NM_001201564.2		c.913-262G>A		intron	N/A	NP_001188493.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLRG1	ENST00000499023.7	TSL:1 MANE Select	c.940-262G>A		intron	N/A	ENSP00000424417.1
	PLRG1	ENST00000302078.9	TSL:1	c.913-262G>A		intron	N/A	ENSP00000303191.5
	PLRG1	ENST00000506627.5	TSL:5	n.253-262G>A		intron	N/A	ENSP00000425914.1

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

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

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.82
DANN	Benign	0.64
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7698829; hg19: chr4-155461467;