rs4375

chr22-38143034-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003560.4(PLA2G6):c.609+71A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,433,638 control chromosomes in the GnomAD database, including 148,246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18628 hom., cov: 31)
  • Exomes 𝑓: 0.44 (129618 hom.)
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.499

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 22-38143034-T-C is Benign according to our data. Variant chr22-38143034-T-C is described in ClinVar as [Benign]. Clinvar id is 1293120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G6	NM_003560.4	c.609+71A>G		intron_variant		ENST00000332509.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G6	ENST00000332509.8	c.609+71A>G		intron_variant		1	NM_003560.4	P3
	ENST00000624072.1	n.12819T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73621 AN: 151794 Hom.: 18612 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.475

GnomAD4 exome AF: 0.445 AC: 570260 AN: 1281726 Hom.: 129618 Cov.: 18 AF XY: 0.449 AC XY: 290189 AN XY: 646784

Gnomad4 AFR exome AF: 0.617

Gnomad4 AMR exome AF: 0.480

Gnomad4 ASJ exome AF: 0.463

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.555

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.485 AC: 73692 AN: 151912 Hom.: 18628 Cov.: 31 AF XY: 0.484 AC XY: 35957 AN XY: 74240

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.478

Alfa AF: 0.460 Hom.: 2763

Bravo AF: 0.494

Asia WGS AF: 0.480 AC: 1673 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	8.5
Dann	Benign	0.79

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: rs4375; hg19: chr22-38539041; COSMIC: COSV59268338; COSMIC: COSV59268338;