rs7069904

Positions:

• chr10-87890081-G-A

Variant summary

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

The NM_000314.8(PTEN):​c.80-3944G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 148,134 control chromosomes in the GnomAD database, including 104 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 0.036 (104 hom., cov: 30)
• Consequence: PTEN NM_000314.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201

Genes affected

PTEN (HGNC:9588): (phosphatase and tensin homolog) This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0361 (5351/148134) while in subpopulation NFE AF= 0.0373 (2514/67340). AF 95% confidence interval is 0.0361. There are 104 homozygotes in gnomad4. There are 2720 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 104 SM gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTEN	NM_000314.8	c.80-3944G>A		intron_variant		ENST00000371953.8	NP_000305.3
PTEN	NM_001304717.5	c.599-3944G>A		intron_variant			NP_001291646.4
PTEN	NM_001304718.2	c.-625-3944G>A		intron_variant			NP_001291647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTEN	ENST00000371953.8	c.80-3944G>A		intron_variant		1	NM_000314.8	ENSP00000361021	P1

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5356 AN: 148032 Hom.: 106 Cov.: 30

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.0519

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.00340

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.0896

Gnomad MID AF: 0.0737

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0371

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

GnomAD4 genome AF: 0.0361 AC: 5351 AN: 148134 Hom.: 104 Cov.: 30 AF XY: 0.0378 AC XY: 2720 AN XY: 71948

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.0242

Gnomad4 ASJ AF: 0.0476

Gnomad4 EAS AF: 0.00341

Gnomad4 SAS AF: 0.0237

Gnomad4 FIN AF: 0.0896

Gnomad4 NFE AF: 0.0373

Gnomad4 OTH AF: 0.0378

Alfa AF: 0.0372 Hom.: 91

Bravo AF: 0.0312

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.65

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: rs7069904; hg19: chr10-89649838;