rs3767221

Variant names:

• chr1-19975288-A-C
• rs3767221
• NM_001395463.1:c.*413T>G

Variant summary

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

The NM_001395463.1(PLA2G2A):​c.*413T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 184,764 control chromosomes in the GnomAD database, including 11,437 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 0.33 (9057 hom., cov: 32)
  • Exomes 𝑓: 0.36 (2380 hom.)
• Consequence: PLA2G2A NM_001395463.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721
• Publications: 7 publications found

Genes affected

PLA2G2A (HGNC:9031): (phospholipase A2 group IIA) The protein encoded by this gene is a member of the phospholipase A2 family (PLA2). PLA2s constitute a diverse family of enzymes with respect to sequence, function, localization, and divalent cation requirements. This gene product belongs to group II, which contains secreted form of PLA2, an extracellular enzyme that has a low molecular mass and requires calcium ions for catalysis. It catalyzes the hydrolysis of the sn-2 fatty acid acyl ester bond of phosphoglycerides, releasing free fatty acids and lysophospholipids, and thought to participate in the regulation of the phospholipid metabolism in biomembranes. Several alternatively spliced transcript variants with different 5' UTRs have been found for this gene.[provided by RefSeq, Sep 2009]

PLA2G2A Gene-Disease associations (from GenCC):

• colorectal cancer

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395463.1. 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
	PLA2G2A	NM_001395463.1	MANE Select	c.*413T>G		downstream_gene	N/A	NP_001382392.1
	PLA2G2A	NM_000300.4		c.*413T>G		downstream_gene	N/A	NP_000291.1
	PLA2G2A	NM_001161727.2		c.*413T>G		downstream_gene	N/A	NP_001155199.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G2A	ENST00000482011.3	TSL:1 MANE Select	c.*413T>G		downstream_gene	N/A	ENSP00000504762.1
	PLA2G2A	ENST00000375111.7	TSL:1	c.*413T>G		downstream_gene	N/A	ENSP00000364252.3
	PLA2G2A	ENST00000400520.8	TSL:1	c.*413T>G		downstream_gene	N/A	ENSP00000383364.3

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49557 AN: 151854 Hom.: 9067 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.364 AC: 11936 AN: 32792 Hom.: 2380 AF XY: 0.367 AC XY: 6259 AN XY: 17058

African (AFR) AF: 0.135 AC: 216 AN: 1600

American (AMR) AF: 0.355 AC: 1215 AN: 3418

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 278 AN: 788

East Asian (EAS) AF: 0.266 AC: 696 AN: 2618

South Asian (SAS) AF: 0.385 AC: 1315 AN: 3416

European-Finnish (FIN) AF: 0.406 AC: 360 AN: 886

Middle Eastern (MID) AF: 0.389 AC: 42 AN: 108

European-Non Finnish (NFE) AF: 0.394 AC: 7258 AN: 18412

Other (OTH) AF: 0.360 AC: 556 AN: 1546

GnomAD4 genome AF: 0.326 AC: 49551 AN: 151972 Hom.: 9057 Cov.: 32 AF XY: 0.332 AC XY: 24640 AN XY: 74264

African (AFR) AF: 0.160 AC: 6612 AN: 41448

American (AMR) AF: 0.327 AC: 4995 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1296 AN: 3464

East Asian (EAS) AF: 0.287 AC: 1485 AN: 5166

South Asian (SAS) AF: 0.408 AC: 1966 AN: 4820

European-Finnish (FIN) AF: 0.488 AC: 5152 AN: 10548

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27073 AN: 67944

Other (OTH) AF: 0.313 AC: 659 AN: 2104

Alfa AF: 0.342 Hom.: 1160

Bravo AF: 0.307

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.81
PhyloP100		-0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3767221; hg19: chr1-20301781;