19-48060277-A-G

Variant names:

• chr19-48060277-A-G
• rs1366444
• NM_003706.3:c.1257+1721T>C

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+1721T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 151,918 control chromosomes in the GnomAD database, including 34,071 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 0.66 (34071 hom., cov: 31)
• Consequence: PLA2G4C NM_003706.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4C	NM_003706.3	MANE Select	c.1257+1721T>C		intron	N/A	NP_003697.2
	PLA2G4C	NM_001159322.2		c.1287+1721T>C		intron	N/A	NP_001152794.1
	PLA2G4C	NM_001159323.2		c.1257+1721T>C		intron	N/A	NP_001152795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4C	ENST00000599921.6	TSL:1 MANE Select	c.1257+1721T>C		intron	N/A	ENSP00000469473.1
	PLA2G4C	ENST00000599111.5	TSL:2	c.1287+1721T>C		intron	N/A	ENSP00000472546.1
	PLA2G4C	ENST00000354276.7	TSL:2	c.1257+1721T>C		intron	N/A	ENSP00000346228.2

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100163 AN: 151800 Hom.: 34058 Cov.: 31

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.657

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.660 AC: 100227 AN: 151918 Hom.: 34071 Cov.: 31 AF XY: 0.667 AC XY: 49487 AN XY: 74248

African (AFR) AF: 0.491 AC: 20335 AN: 41392

American (AMR) AF: 0.757 AC: 11546 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2385 AN: 3470

East Asian (EAS) AF: 0.799 AC: 4099 AN: 5132

South Asian (SAS) AF: 0.701 AC: 3376 AN: 4818

European-Finnish (FIN) AF: 0.823 AC: 8681 AN: 10554

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47514 AN: 67986

Other (OTH) AF: 0.660 AC: 1393 AN: 2110

Alfa AF: 0.684 Hom.: 97493

Bravo AF: 0.646

Asia WGS AF: 0.758 AC: 2636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.16
PhyloP100		-0.67
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: rs1366444; hg19: chr19-48563534;