15-41841265-G-A

Position:

• chr15-41841265-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001114633.2(PLA2G4B):​c.427G>A​(p.Val143Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,612,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: PLA2G4B NM_001114633.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.525

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]

JMJD7-PLA2G4B (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027528465).
• BP6: Variant 15-41841265-G-A is Benign according to our data. Variant chr15-41841265-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3112356.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G4B	NM_001114633.2	c.427G>A	p.Val143Ile	missense_variant	6/20	ENST00000458483.4
JMJD7-PLA2G4B	NM_005090.4	c.1120G>A	p.Val374Ile	missense_variant	11/25
JMJD7-PLA2G4B	NM_001198588.2	c.1120G>A	p.Val374Ile	missense_variant	11/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G4B	ENST00000458483.4	c.427G>A	p.Val143Ile	missense_variant	6/20	2	NM_001114633.2	P1
PLA2G4B	ENST00000452633.5	c.427G>A	p.Val143Ile	missense_variant	7/21	5		P1
PLA2G4B	ENST00000461382.5	n.528G>A		non_coding_transcript_exon_variant	6/10	2

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000173 AC: 43 AN: 248388 Hom.: 0 AF XY: 0.000171 AC XY: 23 AN XY: 134558

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000189

Gnomad NFE exome AF: 0.000288

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000309 AC: 452 AN: 1460648 Hom.: 0 Cov.: 35 AF XY: 0.000283 AC XY: 206 AN XY: 726676

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000453

Gnomad4 NFE exome AF: 0.000371

Gnomad4 OTH exome AF: 0.000149

GnomAD4 genome AF: 0.000328 AC: 50 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22 AN XY: 74454

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000341 Hom.: 0

Bravo AF: 0.000416

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000214 AC: 26

EpiCase AF: 0.000491

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.95
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.56	T;T;.;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.028	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.68	N;N;N;N
REVEL	Benign	0.044
Sift	Benign	0.25	T;T;T;T
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.23	.;.;B;B
Vest4		0.11
MVP		0.030
MPC		0.024
ClinPred		0.013	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.024
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs147786268; hg19: chr15-42133463;