chr15-41841253-G-C

Variant names:

• chr15-41841253-G-C
• rs769124921
• NM_001114633.2:c.415G>C

Variant summary

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

The NM_001114633.2(PLA2G4B):​c.415G>C​(p.Val139Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLA2G4B NM_001114633.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851

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: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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06774771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4B	NM_001114633.2	c.415G>C	p.Val139Leu	missense_variant	Exon 6 of 20	ENST00000458483.4	NP_001108105.1
JMJD7-PLA2G4B	NM_005090.4	c.1108G>C	p.Val370Leu	missense_variant	Exon 11 of 25		NP_005081.1
JMJD7-PLA2G4B	NM_001198588.2	c.1108G>C	p.Val370Leu	missense_variant	Exon 11 of 24		NP_001185517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4B	ENST00000458483.4	c.415G>C	p.Val139Leu	missense_variant	Exon 6 of 20	2	NM_001114633.2	ENSP00000416610.1
JMJD7-PLA2G4B	ENST00000382448.8	c.1108G>C	p.Val370Leu	missense_variant	Exon 11 of 25	2		ENSP00000371886.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000548 AC: 8 AN: 1460670 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 726668

Gnomad4 AFR exome AF: 0.0000299

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: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.12
DANN	Benign	0.78
DEOGEN2	Benign	0.0075	.;.;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.62	T;T;.;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.068	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	.;.;L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.0080
Sift	Benign	0.088	T;T;T;T
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.010	.;.;B;B
Vest4		0.22
MutPred		0.47		.;.;Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.030
MPC		0.028
ClinPred		0.054	T
GERP RS		-6.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs769124921; hg19: chr15-42133451;