chr19-48061950-G-A

Variant names:

• chr19-48061950-G-A
• rs2307276
• NM_003706.3:c.1257+48C>T

Variant summary

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

The NM_003706.3(PLA2G4C):​c.1257+48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,589,648 control chromosomes in the GnomAD database, including 1,419 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 0.055 (342 hom., cov: 31)
  • Exomes 𝑓: 0.034 (1077 hom.)
• Consequence: PLA2G4C NM_003706.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 6 publications found

Genes affected

PLA2G4C (HGNC:9037): (phospholipase A2 group IVC) This gene encodes a protein which is a member of the phospholipase A2 enzyme family which hydrolyzes glycerophospholipids to produce free fatty acids and lysophospholipids, both of which serve as precursors in the production of signaling molecules. The encoded protein has been shown to be a calcium-independent and membrane bound enzyme. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]

PLA2G4C-AS1 (HGNC:51585): (PLA2G4C antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003706.3. 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
	PLA2G4C	NM_003706.3	MANE Select	c.1257+48C>T		intron	N/A	NP_003697.2	Q9UP65-1
	PLA2G4C	NM_001159322.2		c.1287+48C>T		intron	N/A	NP_001152794.1	Q9UP65-3
	PLA2G4C	NM_001159323.2		c.1257+48C>T		intron	N/A	NP_001152795.1	Q9UP65-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4C	ENST00000599921.6	TSL:1 MANE Select	c.1257+48C>T		intron	N/A	ENSP00000469473.1	Q9UP65-1
	PLA2G4C	ENST00000595161.5	TSL:3	c.321+48C>T		intron	N/A	ENSP00000469528.1	M0QY18
	PLA2G4C	ENST00000887096.1		c.1314+48C>T		intron	N/A	ENSP00000557155.1

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8398 AN: 151976 Hom.: 343 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0569

GnomAD2 exomes AF: 0.0329 AC: 7987 AN: 242532 AF XY: 0.0314

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.0259

Gnomad ASJ exome AF: 0.0418

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0131

Gnomad NFE exome AF: 0.0352

Gnomad OTH exome AF: 0.0419

GnomAD4 exome AF: 0.0342 AC: 49167 AN: 1437554 Hom.: 1077 Cov.: 27 AF XY: 0.0334 AC XY: 23917 AN XY: 715850

African (AFR) AF: 0.124 AC: 4037 AN: 32582

American (AMR) AF: 0.0291 AC: 1269 AN: 43680

Ashkenazi Jewish (ASJ) AF: 0.0422 AC: 1088 AN: 25752

East Asian (EAS) AF: 0.00 AC: 0 AN: 38822

South Asian (SAS) AF: 0.0141 AC: 1202 AN: 85350

European-Finnish (FIN) AF: 0.0135 AC: 700 AN: 51790

Middle Eastern (MID) AF: 0.0582 AC: 323 AN: 5552

European-Non Finnish (NFE) AF: 0.0349 AC: 38214 AN: 1094566

Other (OTH) AF: 0.0393 AC: 2334 AN: 59460

GnomAD4 genome AF: 0.0553 AC: 8408 AN: 152094 Hom.: 342 Cov.: 31 AF XY: 0.0532 AC XY: 3957 AN XY: 74344

African (AFR) AF: 0.116 AC: 4794 AN: 41454

American (AMR) AF: 0.0447 AC: 682 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4826

European-Finnish (FIN) AF: 0.0142 AC: 150 AN: 10594

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0352 AC: 2390 AN: 67988

Other (OTH) AF: 0.0563 AC: 119 AN: 2112

Alfa AF: 0.0380 Hom.: 219

Bravo AF: 0.0626

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.90
PhyloP100		-0.51
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: rs2307276; hg19: chr19-48565207;