rs4744

Variant names:

• chr1-19978433-G-A
• rs4744
• NM_001395463.1:c.132C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-19978433-G-A
• chr1-19978433-G-C
• chr1-19978433-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001395463.1(PLA2G2A):​c.132C>T​(p.Tyr44Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,611,986 control chromosomes in the GnomAD database, including 36,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (2794 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33985 hom.)
• Consequence: PLA2G2A NM_001395463.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.456
• Publications: 35 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-19978433-G-A is Benign according to our data. Variant chr1-19978433-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056896.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.456 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2A	NM_001395463.1	c.132C>T	p.Tyr44Tyr	synonymous_variant	Exon 3 of 5	ENST00000482011.3	NP_001382392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.132C>T	p.Tyr44Tyr	synonymous_variant	Exon 3 of 5	1	NM_001395463.1	ENSP00000504762.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26744 AN: 152026 Hom.: 2789 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0240

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.176 AC: 43563 AN: 246998 AF XY: 0.178

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.0900

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.0300

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.208 AC: 304039 AN: 1459840 Hom.: 33985 Cov.: 36 AF XY: 0.207 AC XY: 150044 AN XY: 726290

African (AFR) AF: 0.104 AC: 3476 AN: 33452

American (AMR) AF: 0.0958 AC: 4283 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3498 AN: 26136

East Asian (EAS) AF: 0.0187 AC: 740 AN: 39664

South Asian (SAS) AF: 0.123 AC: 10581 AN: 86226

European-Finnish (FIN) AF: 0.255 AC: 13394 AN: 52510

Middle Eastern (MID) AF: 0.163 AC: 913 AN: 5608

European-Non Finnish (NFE) AF: 0.230 AC: 255725 AN: 1111366

Other (OTH) AF: 0.190 AC: 11429 AN: 60170

GnomAD4 genome AF: 0.176 AC: 26767 AN: 152146 Hom.: 2794 Cov.: 32 AF XY: 0.173 AC XY: 12894 AN XY: 74378

African (AFR) AF: 0.106 AC: 4406 AN: 41524

American (AMR) AF: 0.138 AC: 2113 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3470

East Asian (EAS) AF: 0.0240 AC: 124 AN: 5164

South Asian (SAS) AF: 0.106 AC: 513 AN: 4820

European-Finnish (FIN) AF: 0.240 AC: 2541 AN: 10568

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16025 AN: 67982

Other (OTH) AF: 0.177 AC: 375 AN: 2114

Alfa AF: 0.200 Hom.: 10025

Bravo AF: 0.161

Asia WGS AF: 0.0770 AC: 267 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PLA2G2A-related disorder Benign:1

Oct 25, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.36
PhyloP100		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs4744; hg19: chr1-20304926; COSMIC: COSV64286997;