4-154539617-A-G

Position:

• chr4-154539617-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.1042+334T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,102 control chromosomes in the GnomAD database, including 61,029 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 0.89 (61029 hom., cov: 32)
• Consequence: PLRG1 NM_002669.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLRG1	NM_002669.4	c.1042+334T>C		intron_variant		ENST00000499023.7
PLRG1	NM_001201564.2	c.1015+334T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLRG1	ENST00000499023.7	c.1042+334T>C		intron_variant		1	NM_002669.4	P1
PLRG1	ENST00000302078.9	c.1015+334T>C		intron_variant		1
PLRG1	ENST00000506627.5	c.357+334T>C		intron_variant, NMD_transcript_variant		5
PLRG1	ENST00000507125.1	n.322+334T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135864 AN: 151984 Hom.: 60977 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.898

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

GnomAD4 genome AF: 0.894 AC: 135974 AN: 152102 Hom.: 61029 Cov.: 32 AF XY: 0.893 AC XY: 66353 AN XY: 74340

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.782

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.880

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.898

Alfa AF: 0.885 Hom.: 8529

Bravo AF: 0.902

Asia WGS AF: 0.924 AC: 3174 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.69
DANN	Benign	0.48

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: rs12645631; hg19: chr4-155460769;