chr4-154540842-A-G

Variant names:

• chr4-154540842-A-G
• rs34672135
• NM_002669.4:c.780T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.31
• Publications: 1 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLRG1	NM_002669.4	MANE Select	c.780T>C	p.Tyr260Tyr	synonymous	Exon 9 of 15	NP_002660.1	O43660-1
	PLRG1	NM_001201564.2		c.753T>C	p.Tyr251Tyr	synonymous	Exon 9 of 15	NP_001188493.1	O43660-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLRG1	ENST00000499023.7	TSL:1 MANE Select	c.780T>C	p.Tyr260Tyr	synonymous	Exon 9 of 15	ENSP00000424417.1	O43660-1
	PLRG1	ENST00000302078.9	TSL:1	c.753T>C	p.Tyr251Tyr	synonymous	Exon 9 of 15	ENSP00000303191.5	O43660-2
	PLRG1	ENST00000951251.1		c.840T>C	p.Tyr280Tyr	synonymous	Exon 10 of 16	ENSP00000621310.1

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3935 AN: 152118 Hom.: 157 Cov.: 32

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

GnomAD2 exomes AF: 0.00749 AC: 1880 AN: 251070 AF XY: 0.00570

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 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.: 31 AF XY: 0.00277 AC XY: 2016 AN XY: 726888

African (AFR) AF: 0.0921 AC: 3079 AN: 33434

American (AMR) AF: 0.00613 AC: 274 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00877 AC: 229 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00659 AC: 38 AN: 5768

European-Non Finnish (NFE) AF: 0.000400 AC: 445 AN: 1111362

Other (OTH) AF: 0.00702 AC: 424 AN: 60372

GnomAD4 genome AF: 0.0259 AC: 3941 AN: 152236 Hom.: 157 Cov.: 32 AF XY: 0.0246 AC XY: 1831 AN XY: 74458

African (AFR) AF: 0.0887 AC: 3683 AN: 41520

American (AMR) AF: 0.00837 AC: 128 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000574 AC: 39 AN: 67990

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0121 Hom.: 53

Bravo AF: 0.0299

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000764

EpiControl AF: 0.000948

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.0
DANN	Benign	0.81
PhyloP100		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
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: rs34672135; hg19: chr4-155461994;