rs2053600

Positions:

• chr18-62768548-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000262719.10(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 ENST00000262719.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5064 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLPP1	NM_194449.4	c.1576+51289G>A		intron_variant		ENST00000262719.10	NP_919431.2
LOC105372160	XR_007066397.1	n.146+1359C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHLPP1	ENST00000262719.10	c.1576+51289G>A		intron_variant		1	NM_194449.4	ENSP00000262719	P1

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

Gnomad4 AFR AF: 0.00763

Gnomad4 AMR AF: 0.0268

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.0749

Gnomad4 NFE AF: 0.0487

Gnomad4 OTH AF: 0.0255

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

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: rs2053600; hg19: chr18-60435781;