rs7045881

Variant names:

• chr9-26935998-A-T
• rs7045881
• NM_001031689.3:c.150-792T>A

Variant summary

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

The NM_001031689.3(PLAA):​c.150-792T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,082 control chromosomes in the GnomAD database, including 1,084 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 (1084 hom., cov: 32)
• Consequence: PLAA NM_001031689.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 19 publications found

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]

PLAA Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAA	NM_001031689.3	c.150-792T>A		intron_variant	Intron 1 of 13	ENST00000397292.8	NP_001026859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAA	ENST00000397292.8	c.150-792T>A		intron_variant	Intron 1 of 13	1	NM_001031689.3	ENSP00000380460.3
PLAA	ENST00000520884.5	c.150-792T>A		intron_variant	Intron 1 of 12	2		ENSP00000429372.1
PLAA	ENST00000523212.1	c.87-801T>A		intron_variant	Intron 1 of 5	3		ENSP00000428111.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17139 AN: 151970 Hom.: 1083 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.0804

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.113 AC: 17155 AN: 152082 Hom.: 1084 Cov.: 32 AF XY: 0.114 AC XY: 8451 AN XY: 74336

African (AFR) AF: 0.109 AC: 4510 AN: 41486

American (AMR) AF: 0.0777 AC: 1187 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3472

East Asian (EAS) AF: 0.113 AC: 583 AN: 5176

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4818

European-Finnish (FIN) AF: 0.0804 AC: 848 AN: 10544

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.115 AC: 7820 AN: 68004

Other (OTH) AF: 0.132 AC: 280 AN: 2114

Alfa AF: 0.119 Hom.: 646

Bravo AF: 0.110

Asia WGS AF: 0.162 AC: 565 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.8
DANN	Benign	0.82
PhyloP100		1.3
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: rs7045881; hg19: chr9-26935996;