15-41841252-C-T

Variant names:

• chr15-41841252-C-T
• rs144317980
• NM_001114633.2:c.414C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001114633.2(PLA2G4B):​c.414C>T​(p.Leu138Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,613,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: PLA2G4B NM_001114633.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.70

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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-41841252-C-T is Benign according to our data. Variant chr15-41841252-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645198.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.7 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4B	NM_001114633.2	c.414C>T	p.Leu138Leu	synonymous_variant	Exon 6 of 20	ENST00000458483.4	NP_001108105.1
JMJD7-PLA2G4B	NM_005090.4	c.1107C>T	p.Leu369Leu	synonymous_variant	Exon 11 of 25		NP_005081.1
JMJD7-PLA2G4B	NM_001198588.2	c.1107C>T	p.Leu369Leu	synonymous_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.414C>T	p.Leu138Leu	synonymous_variant	Exon 6 of 20	2	NM_001114633.2	ENSP00000416610.1
JMJD7-PLA2G4B	ENST00000382448.8	c.1107C>T	p.Leu369Leu	synonymous_variant	Exon 11 of 25	2		ENSP00000371886.4

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000277 AC: 69 AN: 248682 Hom.: 0 AF XY: 0.000260 AC XY: 35 AN XY: 134690

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000839

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000243

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000224 AC: 328 AN: 1461256 Hom.: 0 Cov.: 35 AF XY: 0.000243 AC XY: 177 AN XY: 726942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000939

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000213

Gnomad4 OTH exome AF: 0.000232

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74390

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000181 Hom.: 0

Bravo AF: 0.000264

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

JMJD7-PLA2G4B: BP4, BP7; PLA2G4B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.66
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144317980; hg19: chr15-42133450;