22-38204535-C-T

Position:

• chr22-38204535-C-T

Variant summary

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

The NM_012323.4(MAFF):​c.-32+2323C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,906 control chromosomes in the GnomAD database, including 25,875 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 0.58 (25875 hom., cov: 31)
• Consequence: MAFF NM_012323.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAFF	NM_012323.4	c.-32+2323C>T		intron_variant		ENST00000338483.7	NP_036455.1
MAFF	NM_001161572.2	c.-32+2297C>T		intron_variant			NP_001155044.1
MAFF	NM_001161573.1	c.-32+1451C>T		intron_variant			NP_001155045.1
MAFF	NM_001161574.2	c.-52+2323C>T		intron_variant			NP_001155046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAFF	ENST00000338483.7	c.-32+2323C>T		intron_variant		1	NM_012323.4	ENSP00000345393	P1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88245 AN: 151788 Hom.: 25881 Cov.: 31

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.581 AC: 88285 AN: 151906 Hom.: 25875 Cov.: 31 AF XY: 0.577 AC XY: 42803 AN XY: 74234

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.581

Alfa AF: 0.574 Hom.: 24674

Bravo AF: 0.580

Asia WGS AF: 0.490 AC: 1703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2267373; hg19: chr22-38600542;