rs5634

Positions:

• chr12-120325034-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000928.3(PLA2G1B):​c.222T>C​(p.Tyr74Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 1,613,802 control chromosomes in the GnomAD database, including 4,273 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 0.065 (434 hom., cov: 32)
  • Exomes 𝑓: 0.061 (3839 hom.)
• Consequence: PLA2G1B NM_000928.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753

Genes affected

PLA2G1B (HGNC:9030): (phospholipase A2 group IB) This gene encodes a secreted member of the phospholipase A2 (PLA2) class of enzymes, which is produced by the pancreatic acinar cells. The encoded calcium-dependent enzyme catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to release arachidonic acid (AA) and lysophospholipids. AA is subsequently converted by downstream metabolic enzymes to several bioactive lipophilic compounds (eicosanoids), including prostaglandins (PGs) and leukotrienes (LTs). The enzyme may be involved in several physiological processes including cell contraction, cell proliferation and pathological response. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=0.753 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G1B	NM_000928.3	c.222T>C	p.Tyr74Tyr	synonymous_variant	3/4	ENST00000308366.9	NP_000919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G1B	ENST00000308366.9	c.222T>C	p.Tyr74Tyr	synonymous_variant	3/4	1	NM_000928.3	ENSP00000312286.4
PLA2G1B	ENST00000423423.3	c.194+827T>C		intron_variant		1		ENSP00000413594.3
PLA2G1B	ENST00000549767.1	c.135T>C	p.Tyr45Tyr	synonymous_variant	2/3	2		ENSP00000447233.1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9880 AN: 151956 Hom.: 434 Cov.: 32

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.0988

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0488

Gnomad OTH AF: 0.0614

GnomAD3 exomes AF: 0.0833 AC: 20940 AN: 251448 Hom.: 1676 AF XY: 0.0752 AC XY: 10219 AN XY: 135898

Gnomad AFR exome AF: 0.0605

Gnomad AMR exome AF: 0.251

Gnomad ASJ exome AF: 0.0240

Gnomad EAS exome AF: 0.102

Gnomad SAS exome AF: 0.0611

Gnomad FIN exome AF: 0.0593

Gnomad NFE exome AF: 0.0495

Gnomad OTH exome AF: 0.0616

GnomAD4 exome AF: 0.0612 AC: 89507 AN: 1461728 Hom.: 3839 Cov.: 32 AF XY: 0.0600 AC XY: 43615 AN XY: 727186

Gnomad4 AFR exome AF: 0.0597

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.0231

Gnomad4 EAS exome AF: 0.0858

Gnomad4 SAS exome AF: 0.0621

Gnomad4 FIN exome AF: 0.0584

Gnomad4 NFE exome AF: 0.0546

Gnomad4 OTH exome AF: 0.0588

GnomAD4 genome AF: 0.0650 AC: 9886 AN: 152074 Hom.: 434 Cov.: 32 AF XY: 0.0676 AC XY: 5029 AN XY: 74358

Gnomad4 AFR AF: 0.0595

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.0990

Gnomad4 SAS AF: 0.0680

Gnomad4 FIN AF: 0.0656

Gnomad4 NFE AF: 0.0488

Gnomad4 OTH AF: 0.0607

Alfa AF: 0.0520 Hom.: 376

Bravo AF: 0.0723

Asia WGS AF: 0.0830 AC: 286 AN: 3478

EpiCase AF: 0.0438

EpiControl AF: 0.0446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.34

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: rs5634; hg19: chr12-120762837; COSMIC: COSV57679679;