15-41840519-C-T

Position:

• chr15-41840519-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001114633.2(PLA2G4B):​c.83-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000718 in 1,613,684 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0039 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (7 hom.)
• Consequence: PLA2G4B NM_001114633.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00005137
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.977

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:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 15-41840519-C-T is Benign according to our data. Variant chr15-41840519-C-T is described in ClinVar as [Benign]. Clinvar id is 3043511.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4B	NM_001114633.2	c.83-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000458483.4	NP_001108105.1
JMJD7-PLA2G4B	NM_005090.4	c.776-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_005081.1
JMJD7-PLA2G4B	NM_001198588.2	c.776-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001185517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4B	ENST00000458483.4	c.83-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_001114633.2	ENSP00000416610	P1
PLA2G4B	ENST00000452633.5	c.83-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000396045	P1
PLA2G4B	ENST00000461382.5	n.184-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00386 AC: 588 AN: 152168 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000985 AC: 243 AN: 246796 Hom.: 0 AF XY: 0.000777 AC XY: 104 AN XY: 133808

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.000926

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000391 AC: 571 AN: 1461398 Hom.: 7 Cov.: 32 AF XY: 0.000356 AC XY: 259 AN XY: 726984

Gnomad4 AFR exome AF: 0.0138

Gnomad4 AMR exome AF: 0.000380

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000579

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000809

Gnomad4 OTH exome AF: 0.000878

GnomAD4 genome AF: 0.00386 AC: 588 AN: 152286 Hom.: 4 Cov.: 32 AF XY: 0.00395 AC XY: 294 AN XY: 74454

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00189 Hom.: 0

Bravo AF: 0.00424

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PLA2G4B-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.7
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000051
dbscSNV1_RF	Benign	0.0020
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: rs148579102; hg19: chr15-42132717;