chr4-109728735-G-T

Variant names:

• chr4-109728735-G-T
• rs11728699
• NM_030821.5:c.208+867C>A

Variant summary

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

The NM_030821.5(PLA2G12A):​c.208+867C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,096 control chromosomes in the GnomAD database, including 30,716 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 0.62 (30716 hom., cov: 32)
• Consequence: PLA2G12A NM_030821.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 20 publications found

Genes affected

PLA2G12A (HGNC:18554): (phospholipase A2 group XIIA) Secreted phospholipase A2 (sPLA2) enzymes liberate arachidonic acid from phospholipids for production of eicosanoids and exert a variety of physiologic and pathologic effects. Group XII sPLA2s, such as PLA2G12A, have relatively low specific activity and are structurally and functionally distinct from other sPLA2s (Gelb et al., 2000 [PubMed 11031251]).[supplied by OMIM, Mar 2008]

ENSG00000285330 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G12A	NM_030821.5	c.208+867C>A		intron_variant	Intron 1 of 3	ENST00000243501.10	NP_110448.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G12A	ENST00000243501.10	c.208+867C>A		intron_variant	Intron 1 of 3	1	NM_030821.5	ENSP00000243501.5
ENSG00000285330	ENST00000645635.1	c.1535-9976C>A		intron_variant	Intron 12 of 14			ENSP00000493607.1
PLA2G12A	ENST00000502283.1	c.208+867C>A		intron_variant	Intron 1 of 3	1		ENSP00000425274.1
PLA2G12A	ENST00000507961.1	n.208+867C>A		intron_variant	Intron 1 of 2	2		ENSP00000424021.1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94522 AN: 151978 Hom.: 30655 Cov.: 32

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.622 AC: 94644 AN: 152096 Hom.: 30716 Cov.: 32 AF XY: 0.615 AC XY: 45722 AN XY: 74350

African (AFR) AF: 0.818 AC: 33960 AN: 41530

American (AMR) AF: 0.522 AC: 7979 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1638 AN: 3468

East Asian (EAS) AF: 0.361 AC: 1867 AN: 5170

South Asian (SAS) AF: 0.564 AC: 2718 AN: 4822

European-Finnish (FIN) AF: 0.527 AC: 5558 AN: 10554

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.573 AC: 38935 AN: 67960

Other (OTH) AF: 0.582 AC: 1230 AN: 2114

Alfa AF: 0.586 Hom.: 11088

Bravo AF: 0.627

Asia WGS AF: 0.517 AC: 1797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.3
DANN	Benign	0.76
PhyloP100		-0.017
Mutation Taster		=100/0	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: rs11728699; hg19: chr4-110649891;