rs72546340

Variant names:

• chr16-14672308-C-G
• rs72546340
• NM_003561.3:c.*299G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003561.3(PLA2G10):​c.*299G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 152,238 control chromosomes in the GnomAD database, including 25 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 0.015 (25 hom., cov: 32)
• Consequence: PLA2G10 NM_003561.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 1 publications found

Genes affected

PLA2G10 (HGNC:9029): (phospholipase A2 group X) This gene encodes a member of the phospholipase A2 family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature enzyme. This calcium-dependent enzyme hydrolyzes glycerophospholipids to produce free fatty acids and lysophospholipids. In one example, this enzyme catalyzes the release of arachidonic acid from cell membrane phospholipids, thus playing a role in the production of various inflammatory lipid mediators, such as prostaglandins. The encoded protein may promote the survival of breast cancer cells through its role in lipid metabolism. [provided by RefSeq, Nov 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0147 (2243/152238) while in subpopulation NFE AF = 0.0255 (1738/68024). AF 95% confidence interval is 0.0245. There are 25 homozygotes in GnomAd4. There are 993 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G10	NM_003561.3	c.*299G>C		downstream_gene_variant		ENST00000438167.8	NP_003552.1
PLA2G10	NR_133651.1	n.*240G>C		downstream_gene_variant
PLA2G10	XM_047434757.1	c.*299G>C		downstream_gene_variant			XP_047290713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G10	ENST00000438167.8	c.*299G>C		downstream_gene_variant		1	NM_003561.3	ENSP00000393847.4

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2246 AN: 152118 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.00492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00859

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00726

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0147 AC: 2243 AN: 152238 Hom.: 25 Cov.: 32 AF XY: 0.0133 AC XY: 993 AN XY: 74426

African (AFR) AF: 0.00491 AC: 204 AN: 41544

American (AMR) AF: 0.00844 AC: 129 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4822

European-Finnish (FIN) AF: 0.00726 AC: 77 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1738 AN: 68024

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.0191 Hom.: 8

Bravo AF: 0.0150

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.028
DANN	Benign	0.40
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs72546340; hg19: chr16-14766165;