rs141756797

Variant names:

• chr15-41840527-C-A
• rs141756797
• NM_001114633.2:c.86C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-41840527-C-A
• chr15-41840527-C-T

Variant summary

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

The NM_001114633.2(PLA2G4B):​c.86C>A​(p.Thr29Asn) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T29I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G4B NM_001114633.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805

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=0.27990255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4B	NM_001114633.2	c.86C>A	p.Thr29Asn	missense_variant	Exon 3 of 20	ENST00000458483.4	NP_001108105.1
JMJD7-PLA2G4B	NM_005090.4	c.779C>A	p.Thr260Asn	missense_variant	Exon 8 of 25		NP_005081.1
JMJD7-PLA2G4B	NM_001198588.2	c.779C>A	p.Thr260Asn	missense_variant	Exon 8 of 24		NP_001185517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4B	ENST00000458483.4	c.86C>A	p.Thr29Asn	missense_variant	Exon 3 of 20	2	NM_001114633.2	ENSP00000416610.1
JMJD7-PLA2G4B	ENST00000382448.8	c.779C>A	p.Thr260Asn	missense_variant	Exon 8 of 25	2		ENSP00000371886.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.056	.;.;T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.59	T;T;.;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.3	.;.;L;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.037	D;D;D;D
Sift4G	Benign	0.084	T;T;D;D
Polyphen		0.75	.;.;P;P
Vest4		0.42
MutPred		0.42		.;.;Loss of phosphorylation at T29 (P = 0.0375);Loss of phosphorylation at T29 (P = 0.0375);
MVP		0.42
MPC		0.20
ClinPred		0.80	D
GERP RS		4.0
Varity_R		0.072
gMVP		0.34

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

Other links and lift over

dbSNP: rs141756797; hg19: chr15-42132725;