rs775474136

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001114633.2(PLA2G4B):c.283G>A(p.Val95Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PLA2G4B
NM_001114633.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

PLA2G4B (HGNC:9036): (phospholipase A2 group IVB) This gene encodes a member of the cytosolic phospholipase A2 protein family. Phospholipase A2 enzymes hydrolyze the sn-2 bond of phospholipids, releasing lysophospholipids and fatty acids. This enzyme may be associated with mitochondria and early endosomes. Most tissues also express read-through transcripts from the upstream gene into this gene, some of which may encode fusion proteins combining the N-terminus of the upstream gene including its JmjC domain with the almost complete coding region of this gene, including the C2 and cytoplasmic phospholipase A2 domains. [provided by RefSeq, Jul 2008]

PLA2G4B links:

JMJD7-PLA2G4B (HGNC:34449): (JMJD7-PLA2G4B readthrough) This locus represents naturally-occurring readthrough transcription between the neighboring jumonji domain containing 7 (JMJD7) and phospholipase A2, group IVB (cytosolic) (PLA2G4B) genes. Readthrough transcripts encode fusion proteins that share amino acid sequence with each individual gene product, including a partial JmjC domain and downstream C2 and phospholipase A2 domains. Alternatively spliced transcript variants have been observed. [provided by RefSeq, Oct 2013]

JMJD7-PLA2G4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17980605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4B	NM_001114633.2 link	c.283G>A	p.Val95Ile	missense_variant	Exon 4 of 20	ENST00000458483.4	NP_001108105.1	P0C869-1
JMJD7-PLA2G4B	NM_005090.4 link	c.976G>A	p.Val326Ile	missense_variant	Exon 9 of 25		NP_005081.1	P0C869-6
JMJD7-PLA2G4B	NM_001198588.2 link	c.976G>A	p.Val326Ile	missense_variant	Exon 9 of 24		NP_001185517.1	P0C869-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4B	ENST00000458483.4 link	c.283G>A	p.Val95Ile	missense_variant	Exon 4 of 20	2	NM_001114633.2	ENSP00000416610.1		P0C869-1
JMJD7-PLA2G4B	ENST00000382448.8 link	c.976G>A	p.Val326Ile	missense_variant	Exon 9 of 25	2		ENSP00000371886.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248990

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134782

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.976G>A (p.V326I) alteration is located in exon 9 (coding exon 9) of the JMJD7-PLA2G4B gene. This alteration results from a G to A substitution at nucleotide position 976, causing the valine (V) at amino acid position 326 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

.;.;T;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.67

T;T;.;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

.;.;M;M

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.80

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.15

T;T;T;T

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.84

.;.;P;P

Vest4

0.22

MVP

0.092

MPC

0.20

ClinPred

0.44

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.060

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over