chr19-48103405-G-T

Variant names:

• chr19-48103405-G-T
• rs436943
• NM_003706.3:c.257+1183C>A

Variant summary

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

The NM_003706.3(PLA2G4C):​c.257+1183C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,246 control chromosomes in the GnomAD database, including 11,355 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 0.32 (11347 hom., cov: 31)
  • Exomes 𝑓: 0.19 (8 hom.)
• Consequence: PLA2G4C NM_003706.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4C	NM_003706.3	c.257+1183C>A		intron_variant	Intron 4 of 16	ENST00000599921.6	NP_003697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4C	ENST00000599921.6	c.257+1183C>A		intron_variant	Intron 4 of 16	1	NM_003706.3	ENSP00000469473.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48442 AN: 151844 Hom.: 11316 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.190 AC: 54 AN: 284 Hom.: 8 Cov.: 0 AF XY: 0.212 AC XY: 45 AN XY: 212

African (AFR) AF: 0.750 AC: 6 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.167 AC: 2 AN: 12

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.143 AC: 4 AN: 28

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.178 AC: 36 AN: 202

Other (OTH) AF: 0.227 AC: 5 AN: 22

GnomAD4 genome AF: 0.319 AC: 48518 AN: 151962 Hom.: 11347 Cov.: 31 AF XY: 0.315 AC XY: 23374 AN XY: 74276

African (AFR) AF: 0.664 AC: 27471 AN: 41384

American (AMR) AF: 0.225 AC: 3436 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3464

East Asian (EAS) AF: 0.381 AC: 1969 AN: 5164

South Asian (SAS) AF: 0.218 AC: 1053 AN: 4820

European-Finnish (FIN) AF: 0.162 AC: 1709 AN: 10572

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11595 AN: 67986

Other (OTH) AF: 0.279 AC: 590 AN: 2114

Alfa AF: 0.220 Hom.: 2951

Bravo AF: 0.341

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.45
PhyloP100		-0.64
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: rs436943; hg19: chr19-48606662;