15-42079554-A-T

Variant names:

• chr15-42079554-A-T
• rs4924618
• NM_178034.4:c.1300T>A

Variant summary

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

The NM_178034.4(PLA2G4D):​c.1300T>A​(p.Ser434Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,603,226 control chromosomes in the GnomAD database, including 101,491 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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 (8691 hom., cov: 34)
  • Exomes 𝑓: 0.35 (92800 hom.)
• Consequence: PLA2G4D NM_178034.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 26 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.926588E-4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

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.1300T>A	p.Ser434Thr	missense	Exon 13 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.1300T>A	p.Ser434Thr	missense	Exon 13 of 20	ENSP00000290472.3	Q86XP0-1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49213 AN: 151972 Hom.: 8678 Cov.: 34

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.314

GnomAD2 exomes AF: 0.363 AC: 85417 AN: 235162 AF XY: 0.352

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.523

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.428

Gnomad FIN exome AF: 0.432

Gnomad NFE exome AF: 0.356

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.352 AC: 510623 AN: 1451136 Hom.: 92800 Cov.: 45 AF XY: 0.348 AC XY: 251097 AN XY: 722100

African (AFR) AF: 0.180 AC: 5945 AN: 33010

American (AMR) AF: 0.517 AC: 22507 AN: 43516

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 8182 AN: 25954

East Asian (EAS) AF: 0.425 AC: 16667 AN: 39260

South Asian (SAS) AF: 0.238 AC: 20288 AN: 85362

European-Finnish (FIN) AF: 0.437 AC: 21732 AN: 49686

Middle Eastern (MID) AF: 0.222 AC: 1148 AN: 5174

European-Non Finnish (NFE) AF: 0.355 AC: 393553 AN: 1109184

Other (OTH) AF: 0.343 AC: 20601 AN: 59990

GnomAD4 genome AF: 0.324 AC: 49245 AN: 152090 Hom.: 8691 Cov.: 34 AF XY: 0.325 AC XY: 24176 AN XY: 74352

African (AFR) AF: 0.194 AC: 8060 AN: 41484

American (AMR) AF: 0.442 AC: 6761 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3464

East Asian (EAS) AF: 0.420 AC: 2169 AN: 5160

South Asian (SAS) AF: 0.231 AC: 1110 AN: 4814

European-Finnish (FIN) AF: 0.433 AC: 4583 AN: 10586

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24454 AN: 67978

Other (OTH) AF: 0.317 AC: 671 AN: 2114

Alfa AF: 0.349 Hom.: 6381

Bravo AF: 0.324

TwinsUK AF: 0.359 AC: 1333

ALSPAC AF: 0.339 AC: 1305

ESP6500AA AF: 0.196 AC: 864

ESP6500EA AF: 0.347 AC: 2980

ExAC AF: 0.350 AC: 42391

Asia WGS AF: 0.381 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.10	T
MetaRNN	Benign	0.00029	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.47	N
PhyloP100		0.014
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.024
Sift	Benign	0.30	T
Sift4G	Benign	0.38	T
Polyphen		0.17	B
Vest4		0.092
MPC		0.055
ClinPred		0.0034	T
GERP RS		1.3
Varity_R		0.27
gMVP		0.29
Mutation Taster		=96/4	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: rs4924618; hg19: chr15-42371752; COSMIC: COSV51819406; COSMIC: COSV51819406;