18-62768548-G-A

Variant names:

• chr18-62768548-G-A
• rs2053600
• NM_194449.4:c.1576+51289G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_194449.4(PHLPP1):​c.1576+51289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 152,198 control chromosomes in the GnomAD database, including 143 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 0.033 (143 hom., cov: 32)
• Consequence: PHLPP1 NM_194449.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• 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=-0.7).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0333 (5064/152198) while in subpopulation NFE AF = 0.0487 (3311/68008). AF 95% confidence interval is 0.0473. There are 143 homozygotes in GnomAd4. There are 2544 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5064 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLPP1	NM_194449.4	c.1576+51289G>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+51289G>A		intron_variant	Intron 1 of 16	1	NM_194449.4	ENSP00000262719.4

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5064 AN: 152080 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.00766

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0248

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

GnomAD4 genome AF: 0.0333 AC: 5064 AN: 152198 Hom.: 143 Cov.: 32 AF XY: 0.0342 AC XY: 2544 AN XY: 74412

African (AFR) AF: 0.00763 AC: 317 AN: 41524

American (AMR) AF: 0.0268 AC: 409 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00891 AC: 43 AN: 4826

European-Finnish (FIN) AF: 0.0749 AC: 792 AN: 10580

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0487 AC: 3311 AN: 68008

Other (OTH) AF: 0.0255 AC: 54 AN: 2116

Alfa AF: 0.0390 Hom.: 24

Bravo AF: 0.0296

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		0.057
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: rs2053600; hg19: chr18-60435781;