rs12642770

Positions:

• chr4-154539307-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.86).
• 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/exons	MANE	Protein	UniProt
PLRG1	NM_002669.4	c.1043-94A>G		intron_variant		ENST00000499023.7	NP_002660.1
PLRG1	NM_001201564.2	c.1016-94A>G		intron_variant			NP_001188493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLRG1	ENST00000499023.7	c.1043-94A>G		intron_variant		1	NM_002669.4	ENSP00000424417	P1
PLRG1	ENST00000302078.9	c.1016-94A>G		intron_variant		1		ENSP00000303191
PLRG1	ENST00000506627.5	c.358-94A>G		intron_variant, NMD_transcript_variant		5		ENSP00000425914
PLRG1	ENST00000507125.1	n.323-94A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31272 AN: 151972 Hom.: 3795 Cov.: 33

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

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.599

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.206 AC: 31289 AN: 152090 Hom.: 3795 Cov.: 33 AF XY: 0.212 AC XY: 15750 AN XY: 74354

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.202

Alfa AF: 0.203 Hom.: 2761

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
DANN	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs12642770; hg19: chr4-155460459;