rs4608623

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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]

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]

ENSG00000298301 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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+13082C>A		intron	N/A	ENSP00000499555.1	O60733-1
	MAFF	ENST00000852023.1		c.-32+149G>T		intron	N/A	ENSP00000522082.1
	MAFF	ENST00000852024.1		c.-32+43G>T		intron	N/A	ENSP00000522083.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AF: 0.625 AC: 10 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.457 AC: 32 AN: 70

Other (OTH) AF: 0.250 AC: 2 AN: 8

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

African (AFR) AF: 0.449 AC: 18545 AN: 41340

American (AMR) AF: 0.508 AC: 7755 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1895 AN: 3468

East Asian (EAS) AF: 0.501 AC: 2584 AN: 5162

South Asian (SAS) AF: 0.379 AC: 1819 AN: 4804

European-Finnish (FIN) AF: 0.588 AC: 6173 AN: 10492

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37839 AN: 67842

Other (OTH) AF: 0.524 AC: 1104 AN: 2106

Alfa AF: 0.543 Hom.: 16632

Bravo AF: 0.511

Asia WGS AF: 0.427 AC: 1482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.73
PhyloP100		-0.14

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: rs4608623;

hg19: chr22-38597378;