12-120325637-C-A

Variant names:

• chr12-120325637-C-A
• rs2070873
• NM_000928.3:c.194+224G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000928.3(PLA2G1B):​c.194+224G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,230 control chromosomes in the GnomAD database, including 2,594 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 0.17 (2594 hom., cov: 32)
• Consequence: PLA2G1B NM_000928.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930
• Publications: 19 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G1B	NM_000928.3	c.194+224G>T		intron_variant	Intron 2 of 3	ENST00000308366.9	NP_000919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G1B	ENST00000308366.9	c.194+224G>T		intron_variant	Intron 2 of 3	1	NM_000928.3	ENSP00000312286.4
PLA2G1B	ENST00000423423.3	c.194+224G>T		intron_variant	Intron 2 of 2	1		ENSP00000413594.3
PLA2G1B	ENST00000549767.1	c.107+224G>T		intron_variant	Intron 1 of 2	2		ENSP00000447233.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25513 AN: 152112 Hom.: 2591 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0973

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25552 AN: 152230 Hom.: 2594 Cov.: 32 AF XY: 0.171 AC XY: 12731 AN XY: 74414

African (AFR) AF: 0.196 AC: 8126 AN: 41562

American (AMR) AF: 0.152 AC: 2321 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3468

East Asian (EAS) AF: 0.522 AC: 2701 AN: 5170

South Asian (SAS) AF: 0.198 AC: 955 AN: 4822

European-Finnish (FIN) AF: 0.0973 AC: 1031 AN: 10594

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9035 AN: 68008

Other (OTH) AF: 0.164 AC: 347 AN: 2112

Alfa AF: 0.143 Hom.: 3420

Bravo AF: 0.174

Asia WGS AF: 0.290 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.81
PhyloP100		-0.93
PromoterAI		-0.029	Neutral
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2070873; hg19: chr12-120763440; COSMIC: COSV57679571;