rs781465625

Variant names:

• chr1-186854398-C-T
• rs781465625
• NM_024420.3:c.33+11C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-186854398-C-T
• chr1-186854398-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_024420.3(PLA2G4A):​c.33+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,533,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.133
• Publications: 0 publications found

Genes affected

PLA2G4A (HGNC:9035): (phospholipase A2 group IVA) This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to release arachidonic acid which is subsequently metabolized into eicosanoids. Eicosanoids, including prostaglandins and leukotrienes, are lipid-based cellular hormones that regulate hemodynamics, inflammatory responses, and other intracellular pathways. The hydrolysis reaction also produces lysophospholipids that are converted into platelet-activating factor. The enzyme is activated by increased intracellular Ca(2+) levels and phosphorylation, resulting in its translocation from the cytosol and nucleus to perinuclear membrane vesicles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

PLA2G4A Gene-Disease associations (from GenCC):

• cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen
• cryptogenic multifocal ulcerous stenosing enteritis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 1-186854398-C-T is Benign according to our data. Variant chr1-186854398-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3607066.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024420.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4A	NM_024420.3	MANE Select	c.33+11C>T		intron	N/A	NP_077734.2	P47712
	PLA2G4A	NM_001311193.2		c.33+11C>T		intron	N/A	NP_001298122.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4A	ENST00000367466.4	TSL:1 MANE Select	c.33+11C>T		intron	N/A	ENSP00000356436.3	P47712
	PLA2G4A	ENST00000851114.1		c.33+11C>T		intron	N/A	ENSP00000521173.1
	PLA2G4A	ENST00000851115.1		c.33+11C>T		intron	N/A	ENSP00000521174.1

Frequencies

GnomAD3 genomes AF: 0.0000856 AC: 13 AN: 151876 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000116 AC: 29 AN: 250504 AF XY: 0.000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000114 AC: 157 AN: 1381812 Hom.: 0 Cov.: 23 AF XY: 0.000114 AC XY: 79 AN XY: 691976

African (AFR) AF: 0.0000942 AC: 3 AN: 31852

American (AMR) AF: 0.0000225 AC: 1 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25596

East Asian (EAS) AF: 0.00 AC: 0 AN: 39238

South Asian (SAS) AF: 0.00 AC: 0 AN: 84564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 0.000139 AC: 145 AN: 1039478

Other (OTH) AF: 0.000139 AC: 8 AN: 57756

GnomAD4 genome AF: 0.0000856 AC: 13 AN: 151876 Hom.: 0 Cov.: 32 AF XY: 0.0000944 AC XY: 7 AN XY: 74184

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.0000658 AC: 1 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67864

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000217 Hom.: 0

Bravo AF: 0.000102

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		0.13

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: rs781465625; hg19: chr1-186823530;