rs1668589

Positions:

• chr15-42071571-A-G
• chr15-42071571-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178034.4(PLA2G4D):​c.1574-20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 1,601,322 control chromosomes in the GnomAD database, including 467,610 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 0.72 (39631 hom., cov: 30)
  • Exomes 𝑓: 0.77 (427979 hom.)
• Consequence: PLA2G4D NM_178034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

PLA2G4D (HGNC:30038): (phospholipase A2 group IVD) The phospholipase A2 enzyme family, including PLA2G4D, catalyze the hydrolysis of glycerophospholipids at the sn-2 position and then liberate free fatty acids and lysophospholipids (Chiba et al., 2004 [PubMed 14709560]).[supplied by OMIM, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4D	NM_178034.4	c.1574-20T>C		intron_variant		ENST00000290472.4	NP_828848.3
PLA2G4D	XM_047432399.1	c.1574-20T>C		intron_variant			XP_047288355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4D	ENST00000290472.4	c.1574-20T>C		intron_variant		1	NM_178034.4	ENSP00000290472	P1
PLA2G4D	ENST00000560932.1	n.106-20T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108613 AN: 151824 Hom.: 39607 Cov.: 30

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.747

GnomAD3 exomes AF: 0.741 AC: 182530 AN: 246344 Hom.: 68417 AF XY: 0.739 AC XY: 98352 AN XY: 133070

Gnomad AFR exome AF: 0.569

Gnomad AMR exome AF: 0.790

Gnomad ASJ exome AF: 0.796

Gnomad EAS exome AF: 0.590

Gnomad SAS exome AF: 0.641

Gnomad FIN exome AF: 0.785

Gnomad NFE exome AF: 0.788

Gnomad OTH exome AF: 0.762

GnomAD4 exome AF: 0.766 AC: 1110550 AN: 1449380 Hom.: 427979 Cov.: 31 AF XY: 0.763 AC XY: 550399 AN XY: 721336

Gnomad4 AFR exome AF: 0.568

Gnomad4 AMR exome AF: 0.792

Gnomad4 ASJ exome AF: 0.798

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.639

Gnomad4 FIN exome AF: 0.787

Gnomad4 NFE exome AF: 0.785

Gnomad4 OTH exome AF: 0.754

GnomAD4 genome AF: 0.715 AC: 108691 AN: 151942 Hom.: 39631 Cov.: 30 AF XY: 0.717 AC XY: 53280 AN XY: 74258

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.749

Alfa AF: 0.773 Hom.: 68583

Bravo AF: 0.709

Asia WGS AF: 0.655 AC: 2280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1668589; hg19: chr15-42363769; COSMIC: COSV51823951;