NM_002669.4:c.*1229T>C

Variant names:

• chr4-154535456-A-G
• rs7654425
• NM_002669.4:c.*1229T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 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.*1229T>C		3_prime_UTR	Exon 15 of 15	NP_002660.1
	PLRG1	NM_001201564.2		c.*1229T>C		3_prime_UTR	Exon 15 of 15	NP_001188493.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLRG1	ENST00000499023.7	TSL:1 MANE Select	c.*1229T>C		3_prime_UTR	Exon 15 of 15	ENSP00000424417.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.177 AC: 7281 AN: 41034

American (AMR) AF: 0.227 AC: 3413 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1133 AN: 3446

East Asian (EAS) AF: 0.139 AC: 717 AN: 5144

South Asian (SAS) AF: 0.336 AC: 1591 AN: 4736

European-Finnish (FIN) AF: 0.240 AC: 2495 AN: 10416

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22432 AN: 67670

Other (OTH) AF: 0.293 AC: 613 AN: 2090

Alfa AF: 0.308 Hom.: 9718

Bravo AF: 0.259

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.32
PhyloP100		-1.1
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: rs7654425; hg19: chr4-155456608;