22-38202227-A-G

Position:

• chr22-38202227-A-G

Variant summary

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

The NM_012323.4(MAFF):​c.-32+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,292 control chromosomes in the GnomAD database, including 26,912 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 0.59 (26879 hom., cov: 34)
  • Exomes 𝑓: 0.55 (33 hom.)
• Consequence: MAFF NM_012323.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAFF	NM_012323.4	c.-32+15A>G		intron_variant		ENST00000338483.7	NP_036455.1
MAFF	NM_001161572.2	c.-43A>G		5_prime_UTR_variant	1/3		NP_001155044.1
MAFF	NM_001161574.2	c.-52+15A>G		intron_variant			NP_001155046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAFF	ENST00000338483.7	c.-32+15A>G		intron_variant		1	NM_012323.4	ENSP00000345393	P1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 90009 AN: 151938 Hom.: 26887 Cov.: 34

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.600

GnomAD4 exome AF: 0.550 AC: 132 AN: 240 Hom.: 33 Cov.: 0 AF XY: 0.556 AC XY: 99 AN XY: 178

Gnomad4 AFR exome AF: 0.600

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.522

Gnomad4 OTH exome AF: 0.813

GnomAD4 genome AF: 0.592 AC: 90041 AN: 152052 Hom.: 26879 Cov.: 34 AF XY: 0.588 AC XY: 43676 AN XY: 74320

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.595

Alfa AF: 0.596 Hom.: 4206

Bravo AF: 0.590

Asia WGS AF: 0.561 AC: 1942 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2267372; hg19: chr22-38598234;