chr15-41841258-C-T

Variant names:

• chr15-41841258-C-T
• rs377316217
• NM_001114633.2:c.420C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001114633.2(PLA2G4B):​c.420C>T​(p.Ser140Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000906 in 1,613,132 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (21 hom.)
• Consequence: PLA2G4B NM_001114633.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.279
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 15-41841258-C-T is Benign according to our data. Variant chr15-41841258-C-T is described in ClinVar as Benign. ClinVar VariationId is 726643.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.279 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 21 AR gene

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.420C>T	p.Ser140Ser	synonymous	Exon 6 of 20	NP_001108105.1	P0C869-1
	JMJD7-PLA2G4B	NM_005090.4		c.1113C>T	p.Ser371Ser	synonymous	Exon 11 of 25	NP_005081.1
	JMJD7-PLA2G4B	NM_001198588.2		c.1113C>T	p.Ser371Ser	synonymous	Exon 11 of 24	NP_001185517.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4B	ENST00000458483.4	TSL:2 MANE Select	c.420C>T	p.Ser140Ser	synonymous	Exon 6 of 20	ENSP00000416610.1	P0C869-1
	JMJD7-PLA2G4B	ENST00000382448.8	TSL:2	c.1113C>T	p.Ser371Ser	synonymous	Exon 11 of 25	ENSP00000371886.4
	JMJD7-PLA2G4B	ENST00000342159.6	TSL:2	c.1113C>T	p.Ser371Ser	synonymous	Exon 11 of 24	ENSP00000342785.4

Frequencies

GnomAD3 genomes AF: 0.000487 AC: 74 AN: 152044 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00202 AC: 503 AN: 248498 AF XY: 0.00271

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000949 AC: 1387 AN: 1460970 Hom.: 21 Cov.: 35 AF XY: 0.00136 AC XY: 991 AN XY: 726804

African (AFR) AF: 0.000120 AC: 4 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0152 AC: 1309 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5294

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112006

Other (OTH) AF: 0.00109 AC: 66 AN: 60324

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152162 Hom.: 1 Cov.: 32 AF XY: 0.000739 AC XY: 55 AN XY: 74396

African (AFR) AF: 0.0000482 AC: 2 AN: 41512

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000110

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	JMJD7-PLA2G4B-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.0
DANN	Benign	0.60
PhyloP100		0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs377316217; hg19: chr15-42133456;