15-41841521-GG-AA

Variant names:

• chr15-41841521-GG-AA
• NM_001114633.2:c.440_441delGGinsAA
• PLA2G4B p.Arg147Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001114633.2(PLA2G4B):​c.440_441delGGinsAA​(p.Arg147Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PLA2G4B NM_001114633.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114633.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4B	NM_001114633.2	MANE Select	c.440_441delGGinsAA	p.Arg147Gln	missense	N/A	NP_001108105.1	P0C869-1
	JMJD7-PLA2G4B	NM_005090.4		c.1133_1134delGGinsAA	p.Arg378Gln	missense	N/A	NP_005081.1
	JMJD7-PLA2G4B	NM_001198588.2		c.1133_1134delGGinsAA	p.Arg378Gln	missense	N/A	NP_001185517.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4B	ENST00000458483.4	TSL:2 MANE Select	c.440_441delGGinsAA	p.Arg147Gln	missense	N/A	ENSP00000416610.1	P0C869-1
	JMJD7-PLA2G4B	ENST00000382448.8	TSL:2	c.1133_1134delGGinsAA	p.Arg378Gln	missense	N/A	ENSP00000371886.4
	JMJD7-PLA2G4B	ENST00000342159.6	TSL:2	c.1133_1134delGGinsAA	p.Arg378Gln	missense	N/A	ENSP00000342785.4

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-42133719;