12-120325034-A-G

Variant names:

• chr12-120325034-A-G
• rs5634
• NM_000928.3:c.222T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLA2G1B	NM_000928.3	c.222T>C	p.Tyr74Tyr	synonymous_variant	Exon 3 of 4	ENST00000308366.9	NP_000919.1

Ensembl

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

GnomAD2 exomes AF: 0.0833 AC: 20940 AN: 251448 AF XY: 0.0752

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 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

African (AFR) AF: 0.0597 AC: 2000 AN: 33478

American (AMR) AF: 0.236 AC: 10569 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 603 AN: 26134

East Asian (EAS) AF: 0.0858 AC: 3404 AN: 39694

South Asian (SAS) AF: 0.0621 AC: 5354 AN: 86250

European-Finnish (FIN) AF: 0.0584 AC: 3119 AN: 53416

Middle Eastern (MID) AF: 0.0286 AC: 165 AN: 5764

European-Non Finnish (NFE) AF: 0.0546 AC: 60743 AN: 1111894

Other (OTH) AF: 0.0588 AC: 3550 AN: 60392

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

African (AFR) AF: 0.0595 AC: 2469 AN: 41494

American (AMR) AF: 0.151 AC: 2301 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3470

East Asian (EAS) AF: 0.0990 AC: 511 AN: 5162

South Asian (SAS) AF: 0.0680 AC: 328 AN: 4822

European-Finnish (FIN) AF: 0.0656 AC: 695 AN: 10600

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0488 AC: 3318 AN: 67984

Other (OTH) AF: 0.0607 AC: 128 AN: 2108

Alfa AF: 0.0536 Hom.: 524

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
PhyloP100		0.75
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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