rs7654425

Positions:

• chr4-154535456-A-G

Variant summary

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

The NM_002669.4(PLRG1):​c.*1229T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 150,792 control chromosomes in the GnomAD database, including 5,754 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 0.26 (5754 hom., cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLRG1 NM_002669.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLRG1	NM_002669.4	c.*1229T>C		3_prime_UTR_variant	15/15	ENST00000499023.7	NP_002660.1
PLRG1	NM_001201564.2	c.*1229T>C		3_prime_UTR_variant	15/15		NP_001188493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLRG1	ENST00000499023.7	c.*1229T>C		3_prime_UTR_variant	15/15	1	NM_002669.4	ENSP00000424417	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 39937 AN: 150674 Hom.: 5756 Cov.: 29

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.297

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.265 AC: 39924 AN: 150792 Hom.: 5754 Cov.: 29 AF XY: 0.261 AC XY: 19171 AN XY: 73564

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.293

Alfa AF: 0.307 Hom.: 8334

Bravo AF: 0.259

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.32

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: rs7654425; hg19: chr4-155456608;