rs595146

Positions:

• chr18-62785088-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_194449.4(PHLPP1):​c.1577-44947G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 152,264 control chromosomes in the GnomAD database, including 207 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 0.042 (207 hom., cov: 32)
• Consequence: PHLPP1 NM_194449.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52

Genes affected

PHLPP1 (HGNC:20610): (PH domain and leucine rich repeat protein phosphatase 1) This gene encodes a member of the serine/threonine phosphatase family. The encoded protein promotes apoptosis by dephosphorylating and inactivating the serine/threonine kinase Akt, and functions as a tumor suppressor in multiple types of cancer. Increased expression of this gene may also play a role in obesity and type 2 diabetes by interfering with Akt-mediated insulin signaling. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHLPP1	NM_194449.4	c.1577-44947G>A		intron_variant		ENST00000262719.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHLPP1	ENST00000262719.10	c.1577-44947G>A		intron_variant		1	NM_194449.4	P1
PHLPP1	ENST00000497351.5	n.170+5520G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6448 AN: 152146 Hom.: 207 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0314

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.0283

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

GnomAD4 genome AF: 0.0423 AC: 6443 AN: 152264 Hom.: 207 Cov.: 32 AF XY: 0.0408 AC XY: 3034 AN XY: 74454

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0313

Gnomad4 FIN AF: 0.0654

Gnomad4 NFE AF: 0.0664

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0586 Hom.: 350

Bravo AF: 0.0369

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.79

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: rs595146; hg19: chr18-60452321;