15-41840877-G-C

Variant names:

• chr15-41840877-G-C
• rs752705085
• NM_001114633.2:c.323G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001114633.2(PLA2G4B):​c.323G>C​(p.Arg108Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.8e-7 (0 hom.)
• Consequence: PLA2G4B NM_001114633.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34252113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4B	NM_001114633.2	c.323G>C	p.Arg108Pro	missense_variant	Exon 4 of 20	ENST00000458483.4	NP_001108105.1
JMJD7-PLA2G4B	NM_005090.4	c.1016G>C	p.Arg339Pro	missense_variant	Exon 9 of 25		NP_005081.1
JMJD7-PLA2G4B	NM_001198588.2	c.1016G>C	p.Arg339Pro	missense_variant	Exon 9 of 24		NP_001185517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4B	ENST00000458483.4	c.323G>C	p.Arg108Pro	missense_variant	Exon 4 of 20	2	NM_001114633.2	ENSP00000416610.1
JMJD7-PLA2G4B	ENST00000382448.8	c.1016G>C	p.Arg339Pro	missense_variant	Exon 9 of 25	2		ENSP00000371886.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248728 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134658

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: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461438 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726936

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.31
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.011	.;.;T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.68	T;T;.;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	.;.;M;M
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.52	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.29	T;T;T;T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.93	.;.;P;P
Vest4		0.67
MutPred		0.29		.;.;Gain of glycosylation at S113 (P = 0.1169);Gain of glycosylation at S113 (P = 0.1169);
MVP		0.22
MPC		0.052
ClinPred		0.41	T
GERP RS		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs752705085; hg19: chr15-42133075;