15-42070062-G-T

Variant names:

• chr15-42070062-G-T
• rs368349245
• NM_178034.4:c.2077C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178034.4(PLA2G4D):​c.2077C>A​(p.Arg693Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000219 in 1,370,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: PLA2G4D NM_178034.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.73
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178034.4. 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
	PLA2G4D	NM_178034.4	MANE Select	c.2077C>A	p.Arg693Arg	synonymous	Exon 19 of 20	NP_828848.3	Q86XP0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4D	ENST00000290472.4	TSL:1 MANE Select	c.2077C>A	p.Arg693Arg	synonymous	Exon 19 of 20	ENSP00000290472.3	Q86XP0-1
	PLA2G4D	ENST00000560932.1	TSL:1	n.1230C>A		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1370168 Hom.: 0 Cov.: 31 AF XY: 0.00000296 AC XY: 2 AN XY: 675170

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29408

American (AMR) AF: 0.00 AC: 0 AN: 31826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24402

East Asian (EAS) AF: 0.00 AC: 0 AN: 32498

South Asian (SAS) AF: 0.00 AC: 0 AN: 74954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4628

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1067132

Other (OTH) AF: 0.0000176 AC: 1 AN: 56730

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000343967), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.40
PhyloP100		5.7

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: rs368349245; hg19: chr15-42362260;