12-120322275-C-T

Position:

• chr12-120322275-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000928.3(PLA2G1B):​c.365G>A​(p.Arg122His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00069 in 1,613,806 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (6 hom.)
• Consequence: PLA2G1B NM_000928.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.56

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00537923).
• BP6: Variant 12-120322275-C-T is Benign according to our data. Variant chr12-120322275-C-T is described in ClinVar as [Benign]. Clinvar id is 729359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G1B	NM_000928.3	c.365G>A	p.Arg122His	missense_variant	4/4	ENST00000308366.9	NP_000919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G1B	ENST00000308366.9	c.365G>A	p.Arg122His	missense_variant	4/4	1	NM_000928.3	ENSP00000312286.4
PLA2G1B	ENST00000423423	c.*24G>A		3_prime_UTR_variant	3/3	1		ENSP00000413594.3
PLA2G1B	ENST00000549767.1	c.278G>A	p.Arg93His	missense_variant	3/3	2		ENSP00000447233.1

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 462 AN: 152004 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000788

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000887 AC: 223 AN: 251420 Hom.: 2 AF XY: 0.000692 AC XY: 94 AN XY: 135880

Gnomad AFR exome AF: 0.00972

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000325

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000446 AC: 652 AN: 1461684 Hom.: 6 Cov.: 30 AF XY: 0.000396 AC XY: 288 AN XY: 727162

Gnomad4 AFR exome AF: 0.00992

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000201

Gnomad4 OTH exome AF: 0.000861

GnomAD4 genome AF: 0.00303 AC: 461 AN: 152122 Hom.: 4 Cov.: 32 AF XY: 0.00273 AC XY: 203 AN XY: 74360

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.000787

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000633 Hom.: 1

Bravo AF: 0.00350

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0109 AC: 48

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00105 AC: 127

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.50	T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D;D
MetaRNN	Benign	0.0054	T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Pathogenic	4.4	H;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;.
Vest4		0.51
MVP		0.27
MPC		0.42
ClinPred		0.089	T
GERP RS		3.8
Varity_R		0.74
gMVP		0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs151139112; hg19: chr12-120760078;