22-38149612-A-G

Position:

• chr22-38149612-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003560.4(PLA2G6):​c.210-3959T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,016 control chromosomes in the GnomAD database, including 12,402 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 0.40 (12401 hom., cov: 31)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

Genes affected

PLA2G6 (HGNC:9039): (phospholipase A2 group VI) The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G6	NM_003560.4	c.210-3959T>C		intron_variant		ENST00000332509.8	NP_003551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8	c.210-3959T>C		intron_variant		1	NM_003560.4	ENSP00000333142	P3
	ENST00000624072.1	n.19397A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60319 AN: 151892 Hom.: 12378 Cov.: 31

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.397 AC: 60400 AN: 152010 Hom.: 12401 Cov.: 31 AF XY: 0.400 AC XY: 29747 AN XY: 74302

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.381

Alfa AF: 0.366 Hom.: 18586

Bravo AF: 0.401

Asia WGS AF: 0.428 AC: 1490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.73

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: rs6001027; hg19: chr22-38545619;