chr1-186870529-T-A

Variant names:

• chr1-186870529-T-A
• rs67340624
• NM_024420.3:c.115+13T>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.115+13T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21
• Publications: 1 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.91).
• BP6: Variant 1-186870529-T-A is Benign according to our data. Variant chr1-186870529-T-A is described in ClinVar as Benign. ClinVar VariationId is 1895556.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.115+13T>A		intron	N/A	NP_077734.2	P47712
	PLA2G4A	NM_001311193.2		c.115+13T>A		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.115+13T>A		intron	N/A	ENSP00000356436.3	P47712
	PLA2G4A	ENST00000851114.1		c.115+13T>A		intron	N/A	ENSP00000521173.1
	PLA2G4A	ENST00000851115.1		c.115+13T>A		intron	N/A	ENSP00000521174.1

Frequencies

GnomAD3 genomes AF: 0.00335 AC: 474 AN: 141612 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00428

Gnomad AMI AF: 0.00115

Gnomad AMR AF: 0.00173

Gnomad ASJ AF: 0.000598

Gnomad EAS AF: 0.00756

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.00769

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.00204

GnomAD2 exomes AF: 0.00148 AC: 356 AN: 240500 AF XY: 0.00146

Gnomad AFR exome AF: 0.000516

Gnomad AMR exome AF: 0.000303

Gnomad ASJ exome AF: 0.000306

Gnomad EAS exome AF: 0.00232

Gnomad FIN exome AF: 0.00709

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.00202

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000784 AC: 1083 AN: 1381418 Hom.: 3 Cov.: 25 AF XY: 0.000735 AC XY: 508 AN XY: 691088

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000569 AC: 18 AN: 31642

American (AMR) AF: 0.000477 AC: 21 AN: 44020

Ashkenazi Jewish (ASJ) AF: 0.000275 AC: 7 AN: 25460

East Asian (EAS) AF: 0.000911 AC: 35 AN: 38438

South Asian (SAS) AF: 0.000439 AC: 37 AN: 84222

European-Finnish (FIN) AF: 0.00603 AC: 320 AN: 53090

Middle Eastern (MID) AF: 0.000363 AC: 2 AN: 5512

European-Non Finnish (NFE) AF: 0.000558 AC: 581 AN: 1041710

Other (OTH) AF: 0.00108 AC: 62 AN: 57324

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00336 AC: 476 AN: 141706 Hom.: 0 Cov.: 32 AF XY: 0.00346 AC XY: 240 AN XY: 69442

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00433 AC: 164 AN: 37912

American (AMR) AF: 0.00173 AC: 25 AN: 14466

Ashkenazi Jewish (ASJ) AF: 0.000598 AC: 2 AN: 3344

East Asian (EAS) AF: 0.00737 AC: 34 AN: 4614

South Asian (SAS) AF: 0.00460 AC: 20 AN: 4352

European-Finnish (FIN) AF: 0.0138 AC: 129 AN: 9366

Middle Eastern (MID) AF: 0.00806 AC: 2 AN: 248

European-Non Finnish (NFE) AF: 0.00147 AC: 95 AN: 64556

Other (OTH) AF: 0.00202 AC: 4 AN: 1978

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0112 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.91
CADD	Benign	0.20
DANN	Benign	0.61
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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: rs67340624; hg19: chr1-186839661;