Genetic Variant PLRG1:p.Tyr260Tyr (chr4-154540842-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002669.4(PLRG1):c.780T>C(p.Tyr260Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.00524 in 1,613,346 control chromosomes in the GnomAD database, including 296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 157 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 139 hom. )

Consequence

PLRG1
NM_002669.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.31

Variant links:

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]

PLRG1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 4-154540842-A-G is Benign according to our data. Variant chr4-154540842-A-G is described in ClinVar as [Benign]. Clinvar id is 767980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLRG1	NM_002669.4 link	c.780T>C	p.Tyr260Tyr	synonymous_variant	Exon 9 of 15	ENST00000499023.7	NP_002660.1	O43660-1
PLRG1	NM_001201564.2 link	c.753T>C	p.Tyr251Tyr	synonymous_variant	Exon 9 of 15		NP_001188493.1	O43660-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLRG1	ENST00000499023.7 link	c.780T>C	p.Tyr260Tyr	synonymous_variant	Exon 9 of 15	1	NM_002669.4	ENSP00000424417.1		O43660-1

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3935

AN:

152118

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0888

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00845

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000574

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.00749

AC:

1880

AN:

251070

Hom.:

AF XY:

0.00570

AC XY:

773

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.0920

Gnomad AMR exome

AF:

0.00556

Gnomad ASJ exome

AF:

0.00924

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000494

Gnomad OTH exome

AF:

0.00637

GnomAD4 exome

AF:

0.00309

AC:

4509

AN:

1461110

Hom.:

139

Cov.:

AF XY:

0.00277

AC XY:

2016

AN XY:

726888

show subpopulations

Gnomad4 AFR exome

AF:

0.0921

Gnomad4 AMR exome

AF:

0.00613

Gnomad4 ASJ exome

AF:

0.00877

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000400

Gnomad4 OTH exome

AF:

0.00702

GnomAD4 genome

AF:

0.0259

AC:

3941

AN:

152236

Hom.:

157

Cov.:

AF XY:

0.0246

AC XY:

1831

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0887

Gnomad4 AMR

AF:

0.00837

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000574

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.0299

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.000764

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 08, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.0

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over