dbSNP rs4375: PLA2G6:c.609+71A>G (chr22-38143034-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.499

Variant links:

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]

PLA2G6 links:

ENSG00000279080 (HGNC:):

ENSG00000279080 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
PLA2G6	NM_003560.4 link	c.609+71A>G		intron_variant	Intron 4 of 16	ENST00000332509.8	NP_003551.2	O60733-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8 link	c.609+71A>G		intron_variant	Intron 4 of 16	1	NM_003560.4	ENSP00000333142.3		O60733-1

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73621

AN:

151794

Hom.:

18612

Cov.:

show subpopulations

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.:

AF XY:

0.449

AC XY:

290189

AN XY:

646784

show subpopulations

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.:

AF XY:

0.484

AC XY:

35957

AN XY:

74240

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 38% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 35. Only high quality variants are reported. -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over