rs12003612

chr9-26940725-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031689.3(PLAA):c.150-5519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,088 control chromosomes in the GnomAD database, including 1,108 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 0.11 (1108 hom., cov: 32)
• Consequence: PLAA NM_001031689.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423

Genes affected

PLAA (HGNC:9043): (phospholipase A2 activating protein) Predicted to enable ubiquitin binding activity. Involved in cellular response to lipopolysaccharide; macroautophagy; and positive regulation of phospholipase A2 activity. Located in cytoplasm; extracellular exosome; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -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 = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAA	NM_001031689.3	c.150-5519G>A		intron_variant		ENST00000397292.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAA	ENST00000397292.8	c.150-5519G>A		intron_variant		1	NM_001031689.3	P1
PLAA	ENST00000520884.5	c.150-5519G>A		intron_variant		2
PLAA	ENST00000523212.1	c.88-5528G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17378 AN: 151970 Hom.: 1104 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0760

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0940

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.114 AC: 17410 AN: 152088 Hom.: 1108 Cov.: 32 AF XY: 0.112 AC XY: 8347 AN XY: 74314

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0267

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0760

Gnomad4 NFE AF: 0.0940

Gnomad4 OTH AF: 0.118

Alfa AF: 0.101 Hom.: 1044

Bravo AF: 0.116

Asia WGS AF: 0.0930 AC: 324 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	7.1
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: rs12003612; hg19: chr9-26940723;