rs3761445

Variant names:

• chr22-38199404-G-A
• rs3761445
• ENST00000660610.1:c.-42+15049C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-38199404-G-A
• chr22-38199404-G-C

Variant summary

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

The ENST00000594306.1(PLA2G6):​c.-46+5889C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,858 control chromosomes in the GnomAD database, including 21,961 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 0.53 (21961 hom., cov: 30)
• Consequence: PLA2G6 ENST00000594306.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430
• Publications: 34 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: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• neurodegeneration with brain iron accumulation 2B

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

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

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

ENSG00000298301 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 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.-42+15049C>T		intron	N/A	ENSP00000499555.1
	PLA2G6	ENST00000594306.1	TSL:4	c.-46+5889C>T		intron	N/A	ENSP00000473160.1
	ENSG00000298301	ENST00000754572.1		n.184+3882C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79825 AN: 151740 Hom.: 21978 Cov.: 30

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.526 AC: 79838 AN: 151858 Hom.: 21961 Cov.: 30 AF XY: 0.525 AC XY: 38919 AN XY: 74176

African (AFR) AF: 0.366 AC: 15153 AN: 41422

American (AMR) AF: 0.516 AC: 7860 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3472

East Asian (EAS) AF: 0.739 AC: 3811 AN: 5160

South Asian (SAS) AF: 0.457 AC: 2201 AN: 4814

European-Finnish (FIN) AF: 0.610 AC: 6409 AN: 10502

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40687 AN: 67938

Other (OTH) AF: 0.540 AC: 1138 AN: 2108

Alfa AF: 0.581 Hom.: 23359

Bravo AF: 0.518

Asia WGS AF: 0.553 AC: 1919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.58
PhyloP100		-0.43

Splicing

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

Other links and lift over

dbSNP: rs3761445; hg19: chr22-38595411;