rs3761444

Variant names:

• chr22-38184364-G-A
• rs3761444
• ENST00000660610.1:c.-41-14897C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-38184364-G-A
• chr22-38184364-G-T

Variant summary

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

The ENST00000594306.1(PLA2G6):​c.-45-14893C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,048 control chromosomes in the GnomAD database, including 20,025 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 0.50 (20025 hom., cov: 32)
• Consequence: PLA2G6 ENST00000594306.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• neurodegeneration with brain iron accumulation 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics, Genomics England PanelApp
• neurodegeneration with brain iron accumulation 2B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• PLA2G6-associated neurodegeneration

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive Parkinson disease 14

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

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 (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000594306.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G6	ENST00000660610.1		c.-41-14897C>T		intron	N/A	ENSP00000499555.1	O60733-1
	PLA2G6	ENST00000885143.1		c.-46+7669C>T		intron	N/A	ENSP00000555202.1
	PLA2G6	ENST00000955628.1		c.-46+7669C>T		intron	N/A	ENSP00000625687.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76537 AN: 151928 Hom.: 20034 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.503 AC: 76545 AN: 152048 Hom.: 20025 Cov.: 32 AF XY: 0.502 AC XY: 37290 AN XY: 74314

African (AFR) AF: 0.381 AC: 15804 AN: 41456

American (AMR) AF: 0.503 AC: 7681 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1853 AN: 3472

East Asian (EAS) AF: 0.601 AC: 3107 AN: 5170

South Asian (SAS) AF: 0.370 AC: 1781 AN: 4816

European-Finnish (FIN) AF: 0.600 AC: 6349 AN: 10574

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38425 AN: 67974

Other (OTH) AF: 0.523 AC: 1103 AN: 2110

Alfa AF: 0.665 Hom.: 6449

Bravo AF: 0.496

Asia WGS AF: 0.456 AC: 1583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.25
DANN	Benign	0.39
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3761444;

hg19: chr22-38580371;