rs4374456

Positions:

• chr22-38201370-G-C
• chr22-38201370-G-T

Variant summary

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

The ENST00000660610.1(PLA2G6):​c.-42+13083C>G 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 151,770 control chromosomes in the GnomAD database, including 20,422 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 (20411 hom., cov: 31)
  • Exomes 𝑓: 0.44 (11 hom.)
• Consequence: PLA2G6 ENST00000660610.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346

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=-0.86).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G6	ENST00000594306.1	c.-46+3923C>G		intron_variant		4
PLA2G6	ENST00000660610.1	c.-42+13083C>G		intron_variant				P3
MAFF	ENST00000624676.1	n.604G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78098 AN: 151546 Hom.: 20413 Cov.: 31

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.356

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: 0.443 AC: 47 AN: 106 Hom.: 11 Cov.: 0 AF XY: 0.412 AC XY: 33 AN XY: 80

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.515 AC: 78134 AN: 151664 Hom.: 20411 Cov.: 31 AF XY: 0.512 AC XY: 37955 AN XY: 74072

Gnomad4 AFR AF: 0.448

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: 0.532 Hom.: 2629

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	-0.86
CADD	Benign	5.3
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4374456; hg19: chr22-38597377;