22-38215073-C-G

Position:

• chr22-38215073-C-G

Variant summary

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

The NM_012323.4(MAFF):​c.*195C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 534,336 control chromosomes in the GnomAD database, including 58,280 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 0.41 (14020 hom., cov: 31)
  • Exomes 𝑓: 0.47 (44260 hom.)
• Consequence: MAFF NM_012323.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAFF	NM_012323.4	c.*195C>G		3_prime_UTR_variant	3/3	ENST00000338483.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAFF	ENST00000338483.7	c.*195C>G		3_prime_UTR_variant	3/3	1	NM_012323.4	P1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62106 AN: 151776 Hom.: 14032 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.436

GnomAD3 exomes AF: 0.485 AC: 18364 AN: 37870 Hom.: 4627 AF XY: 0.480 AC XY: 9440 AN XY: 19656

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.515

Gnomad ASJ exome AF: 0.513

Gnomad EAS exome AF: 0.447

Gnomad SAS exome AF: 0.332

Gnomad FIN exome AF: 0.541

Gnomad NFE exome AF: 0.494

Gnomad OTH exome AF: 0.499

GnomAD4 exome AF: 0.473 AC: 180780 AN: 382442 Hom.: 44260 Cov.: 4 AF XY: 0.466 AC XY: 95070 AN XY: 204134

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.551

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.461

GnomAD4 genome AF: 0.409 AC: 62103 AN: 151894 Hom.: 14020 Cov.: 31 AF XY: 0.411 AC XY: 30503 AN XY: 74218

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.432

Alfa AF: 0.361 Hom.: 1871

Bravo AF: 0.398

Asia WGS AF: 0.378 AC: 1310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9610915; hg19: chr22-38611080; COSMIC: COSV58298787; COSMIC: COSV58298787;