dbSNP rs7416510: PLA2G4A:c.33+20T>C (chr1-186854407-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_024420.3(PLA2G4A):c.33+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,510,842 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

PLA2G4A
NM_024420.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

Publications

0 publications found

Variant links:

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

PLA2G4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-186854407-T-C is Benign according to our data. Variant chr1-186854407-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1900330.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+20T>C		intron	N/A	NP_077734.2	P47712
	PLA2G4A	NM_001311193.2		c.33+20T>C		intron	N/A	NP_001298122.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLA2G4A	ENST00000367466.4	TSL:1 MANE Select	c.33+20T>C	intron	N/A	ENSP00000356436.3	P47712
PLA2G4A	ENST00000851114.1		c.33+20T>C	intron	N/A	ENSP00000521173.1
PLA2G4A	ENST00000851115.1		c.33+20T>C	intron	N/A	ENSP00000521174.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000759

AC:

AN:

250478

AF XY:

0.0000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000552

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1358864

Hom.:

Cov.:

AF XY:

0.0000161

AC XY:

AN XY:

682152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31408

American (AMR)

AF:

0.000630

AC:

AN:

44460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25460

East Asian (EAS)

AF:

0.00

AC:

AN:

39134

South Asian (SAS)

AF:

0.00

AC:

AN:

84156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5562

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1018524

Other (OTH)

AF:

0.00

AC:

AN:

56934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151978

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41422

American (AMR)

AF:

0.000131

AC:

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67912

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000378

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over