4-154534837-C-T

Variant names:

• chr4-154534837-C-T
• rs13122184
• NM_002669.4:c.*1848G>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.*1848G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 151,944 control chromosomes in the GnomAD database, including 148 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 0.035 (148 hom., cov: 31)
• Consequence: PLRG1 NM_002669.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLRG1	NM_002669.4	c.*1848G>A		downstream_gene_variant		ENST00000499023.7	NP_002660.1
PLRG1	NM_001201564.2	c.*1848G>A		downstream_gene_variant			NP_001188493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLRG1	ENST00000499023.7	c.*1848G>A		downstream_gene_variant		1	NM_002669.4	ENSP00000424417.1

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5389 AN: 151824 Hom.: 147 Cov.: 31

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.0168

Gnomad MID AF: 0.0584

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0451

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0355 AC: 5388 AN: 151944 Hom.: 148 Cov.: 31 AF XY: 0.0338 AC XY: 2510 AN XY: 74294

African (AFR) AF: 0.0105 AC: 435 AN: 41464

American (AMR) AF: 0.0347 AC: 528 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0441 AC: 212 AN: 4810

European-Finnish (FIN) AF: 0.0168 AC: 177 AN: 10554

Middle Eastern (MID) AF: 0.0590 AC: 17 AN: 288

European-Non Finnish (NFE) AF: 0.0560 AC: 3805 AN: 67930

Other (OTH) AF: 0.0437 AC: 92 AN: 2106

Alfa AF: 0.0116 Hom.: 3

Bravo AF: 0.0357

Asia WGS AF: 0.0160 AC: 58 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	1.1
DANN	Benign	0.64
PhyloP100		-0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13122184; hg19: chr4-155455989;