chr18-62773567-T-A

Variant names:

• chr18-62773567-T-A
• rs9958800
• NM_194449.4:c.1576+56308T>A

Variant summary

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

The NM_194449.4(PHLPP1):​c.1576+56308T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,120 control chromosomes in the GnomAD database, including 6,832 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 0.24 (6832 hom., cov: 32)
• Consequence: PHLPP1 NM_194449.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 3 publications found

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]

LOC105372160 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLPP1	NM_194449.4	c.1576+56308T>A		intron_variant	Intron 1 of 16	ENST00000262719.10	NP_919431.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLPP1	ENST00000262719.10	c.1576+56308T>A		intron_variant	Intron 1 of 16	1	NM_194449.4	ENSP00000262719.4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35863 AN: 152002 Hom.: 6794 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0795

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.236 AC: 35958 AN: 152120 Hom.: 6832 Cov.: 32 AF XY: 0.231 AC XY: 17144 AN XY: 74374

African (AFR) AF: 0.531 AC: 22006 AN: 41440

American (AMR) AF: 0.124 AC: 1894 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3464

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5178

South Asian (SAS) AF: 0.0796 AC: 384 AN: 4826

European-Finnish (FIN) AF: 0.154 AC: 1636 AN: 10608

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8829 AN: 67998

Other (OTH) AF: 0.208 AC: 440 AN: 2114

Alfa AF: 0.196 Hom.: 588

Bravo AF: 0.249

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		-0.13
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: rs9958800; hg19: chr18-60440800;