18-9590436-G-C

Variant names:

• chr18-9590436-G-C
• rs7239728
• NM_001042388.3:c.296-1583C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042388.3(PPP4R1):​c.296-1583C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,016 control chromosomes in the GnomAD database, including 11,200 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 0.37 (11200 hom., cov: 32)
• Consequence: PPP4R1 NM_001042388.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 3 publications found

Genes affected

PPP4R1 (HGNC:9320): (protein phosphatase 4 regulatory subunit 1) This gene encodes one of several alternate regulatory subunits of serine/threonine protein phosphatase 4 (PP4). The protein features multiple HEAT repeats. This protein forms a complex with PP4RC. This complex may have a distinct role from other PP4 complexes, including regulation of HDAC3 (Zhang et al., PMID: 15805470). There is also a transcribed pseudogene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042388.3. 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
	PPP4R1	NM_001042388.3	MANE Select	c.296-1583C>G		intron	N/A	NP_001035847.1
	PPP4R1	NM_005134.4		c.245-1583C>G		intron	N/A	NP_005125.1
	PPP4R1	NM_001382562.1		c.29-1583C>G		intron	N/A	NP_001369491.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP4R1	ENST00000400556.8	TSL:1 MANE Select	c.296-1583C>G		intron	N/A	ENSP00000383402.3
	PPP4R1	ENST00000400555.7	TSL:1	c.245-1583C>G		intron	N/A	ENSP00000383401.3
	PPP4R1	ENST00000582240.5	TSL:4	c.401-1583C>G		intron	N/A	ENSP00000463909.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55468 AN: 151898 Hom.: 11172 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.365 AC: 55548 AN: 152016 Hom.: 11200 Cov.: 32 AF XY: 0.369 AC XY: 27393 AN XY: 74320

African (AFR) AF: 0.529 AC: 21949 AN: 41460

American (AMR) AF: 0.327 AC: 4987 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 905 AN: 3464

East Asian (EAS) AF: 0.541 AC: 2795 AN: 5164

South Asian (SAS) AF: 0.410 AC: 1976 AN: 4824

European-Finnish (FIN) AF: 0.291 AC: 3065 AN: 10550

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18591 AN: 67966

Other (OTH) AF: 0.332 AC: 700 AN: 2108

Alfa AF: 0.320 Hom.: 1064

Bravo AF: 0.371

Asia WGS AF: 0.415 AC: 1443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.50
PhyloP100		-0.87
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: rs7239728; hg19: chr18-9590434;