15-41842325-C-T

Variant names:

• chr15-41842325-C-T
• rs1648833
• NM_001114633.2:c.705+49C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001114633.2(PLA2G4B):​c.705+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,608,608 control chromosomes in the GnomAD database, including 512,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (44409 hom., cov: 32)
  • Exomes 𝑓: 0.80 (468203 hom.)
• Consequence: PLA2G4B NM_001114633.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4B	NM_001114633.2	c.705+49C>T		intron_variant	Intron 9 of 19	ENST00000458483.4	NP_001108105.1
JMJD7-PLA2G4B	NM_005090.4	c.1398+49C>T		intron_variant	Intron 14 of 24		NP_005081.1
JMJD7-PLA2G4B	NM_001198588.2	c.1398+49C>T		intron_variant	Intron 14 of 23		NP_001185517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4B	ENST00000458483.4	c.705+49C>T		intron_variant	Intron 9 of 19	2	NM_001114633.2	ENSP00000416610.1
JMJD7-PLA2G4B	ENST00000382448.8	c.1398+49C>T		intron_variant	Intron 14 of 24	2		ENSP00000371886.4

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115261 AN: 151910 Hom.: 44381 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.768

GnomAD2 exomes AF: 0.804 AC: 194271 AN: 241764 AF XY: 0.802

Gnomad AFR exome AF: 0.613

Gnomad AMR exome AF: 0.847

Gnomad ASJ exome AF: 0.877

Gnomad EAS exome AF: 0.875

Gnomad FIN exome AF: 0.835

Gnomad NFE exome AF: 0.811

Gnomad OTH exome AF: 0.822

GnomAD4 exome AF: 0.800 AC: 1165688 AN: 1456580 Hom.: 468203 Cov.: 40 AF XY: 0.799 AC XY: 579143 AN XY: 724424

African (AFR) AF: 0.604 AC: 20069 AN: 33224

American (AMR) AF: 0.845 AC: 37061 AN: 43878

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 22689 AN: 25946

East Asian (EAS) AF: 0.883 AC: 35004 AN: 39650

South Asian (SAS) AF: 0.731 AC: 62797 AN: 85962

European-Finnish (FIN) AF: 0.834 AC: 43746 AN: 52444

Middle Eastern (MID) AF: 0.819 AC: 4572 AN: 5582

European-Non Finnish (NFE) AF: 0.803 AC: 891151 AN: 1109842

Other (OTH) AF: 0.809 AC: 48599 AN: 60052

GnomAD4 genome AF: 0.759 AC: 115334 AN: 152028 Hom.: 44409 Cov.: 32 AF XY: 0.761 AC XY: 56546 AN XY: 74306

African (AFR) AF: 0.617 AC: 25543 AN: 41432

American (AMR) AF: 0.818 AC: 12508 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3066 AN: 3470

East Asian (EAS) AF: 0.873 AC: 4493 AN: 5146

South Asian (SAS) AF: 0.738 AC: 3546 AN: 4808

European-Finnish (FIN) AF: 0.833 AC: 8827 AN: 10602

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54807 AN: 67968

Other (OTH) AF: 0.772 AC: 1631 AN: 2112

Alfa AF: 0.794 Hom.: 23682

Bravo AF: 0.754

Asia WGS AF: 0.810 AC: 2816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.7
DANN	Benign	0.76
PhyloP100		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1648833; hg19: chr15-42134523;