dbSNP rs5634: PLA2G1B:p.Tyr74Tyr (chr12-120325034-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.753

Publications

25 publications found

Variant links:

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]

PLA2G1B links:

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ACMG classification

Classification was made for transcript

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 link	c.222T>C	p.Tyr74Tyr	synonymous_variant	Exon 3 of 4	ENST00000308366.9	NP_000919.1	P04054

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLA2G1B	ENST00000308366.9 link	c.222T>C	p.Tyr74Tyr	synonymous_variant	Exon 3 of 4	1	NM_000928.3	ENSP00000312286.4	P04054
PLA2G1B	ENST00000423423.3 link	c.194+827T>C		intron_variant	Intron 2 of 2	1		ENSP00000413594.3	Q9BS22
PLA2G1B	ENST00000549767.1 link	c.135T>C	p.Tyr45Tyr	synonymous_variant	Exon 2 of 3	2		ENSP00000447233.1	F8W062

Frequencies

GnomAD3 genomes

AF:

0.0650

AC:

9880

AN:

151956

Hom.:

434

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0600

AC XY:

43615

AN XY:

727186

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

4066

8132

12198

16264

20330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2520

5040

7560

10080

12600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0650

AC:

9886

AN:

152074

Hom.:

434

Cov.:

AF XY:

0.0676

AC XY:

5029

AN XY:

74358

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0488

AC:

3318

AN:

67984

Other (OTH)

AF:

0.0607

AC:

128

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

458

917

1375

1834

2292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.34

PhyloP100

0.75

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over