22-38201371-G-T

Variant names:

• chr22-38201371-G-T
• rs4608623
• ENST00000660610.1:c.-42+13082C>A

Variant summary

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

The ENST00000594306.1(PLA2G6):​c.-46+3922C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,788 control chromosomes in the GnomAD database, including 20,436 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 0.52 (20425 hom., cov: 31)
  • Exomes 𝑓: 0.45 (11 hom.)
• Consequence: PLA2G6 ENST00000594306.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

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]

MAFF (HGNC:6780): (MAF bZIP transcription factor F) The protein encoded by this gene is a basic leucine zipper (bZIP) transcription factor that lacks a transactivation domain. It is known to bind the US-2 DNA element in the promoter of the oxytocin receptor (OTR) gene and most likely heterodimerizes with other leucine zipper-containing proteins to enhance expression of the OTR gene during term pregnancy. The encoded protein can also form homodimers, and since it lacks a transactivation domain, the homodimer may act as a repressor of transcription. This gene may also be involved in the cellular stress response. Multiple transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000660610.1	c.-42+13082C>A		intron_variant	Intron 1 of 16			ENSP00000499555.1
PLA2G6	ENST00000594306.1	c.-46+3922C>A		intron_variant	Intron 1 of 1	4		ENSP00000473160.1
MAFF	ENST00000624676.1	n.605G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78125 AN: 151566 Hom.: 20427 Cov.: 31

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.452 AC: 47 AN: 104 Hom.: 11 Cov.: 0 AF XY: 0.423 AC XY: 33 AN XY: 78

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.515 AC: 78161 AN: 151684 Hom.: 20425 Cov.: 31 AF XY: 0.512 AC XY: 37974 AN XY: 74100

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.524

Alfa AF: 0.545 Hom.: 8507

Bravo AF: 0.511

Asia WGS AF: 0.427 AC: 1482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4608623; hg19: chr22-38597378;