rs151139112

Variant names:

• chr12-120322275-C-A
• rs151139112
• NM_000928.3:c.365G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-120322275-C-A
• chr12-120322275-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000928.3(PLA2G1B):​c.365G>T​(p.Arg122Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PLA2G1B NM_000928.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26706964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G1B	NM_000928.3	c.365G>T	p.Arg122Leu	missense_variant	Exon 4 of 4	ENST00000308366.9	NP_000919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G1B	ENST00000308366.9	c.365G>T	p.Arg122Leu	missense_variant	Exon 4 of 4	1	NM_000928.3	ENSP00000312286.4
PLA2G1B	ENST00000423423	c.*24G>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000413594.3
PLA2G1B	ENST00000549767.1	c.278G>T	p.Arg93Leu	missense_variant	Exon 3 of 3	2		ENSP00000447233.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461684 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.078
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Benign	0.17
Sift	Benign	0.28	T;T
Sift4G	Uncertain	0.052	T;D
Polyphen		0.53	P;.
Vest4		0.33
MutPred		0.63		Gain of catalytic residue at D121 (P = 0);.;
MVP		0.26
MPC		0.25
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.50
gMVP		0.85

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;