16-79594427-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005360.5(MAF):c.*32del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 1,529,704 control chromosomes in the GnomAD database, including 5,585 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (428 hom., cov: 31)
  • Exomes 𝑓: 0.083 (5157 hom.)
• Consequence: MAF NM_005360.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.852

Genes affected

MAF (HGNC:6776): (MAF bZIP transcription factor) The protein encoded by this gene is a DNA-binding, leucine zipper-containing transcription factor that acts as a homodimer or as a heterodimer. Depending on the binding site and binding partner, the encoded protein can be a transcriptional activator or repressor. This protein plays a role in the regulation of several cellular processes, including embryonic lens fiber cell development, increased T-cell susceptibility to apoptosis, and chondrocyte terminal differentiation. Defects in this gene are a cause of juvenile-onset pulverulent cataract as well as congenital cerulean cataract 4 (CCA4). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-79594427-GA-G is Benign according to our data. Variant chr16-79594427-GA-G is described in ClinVar as [Benign]. Clinvar id is 1236763.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAF	NM_005360.5	c.*32del		3_prime_UTR_variant	2/2	ENST00000326043.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAF	ENST00000326043.5	c.*32del		3_prime_UTR_variant	2/2	1	NM_005360.5	A2
MAF	ENST00000393350.1	c.*4353del		3_prime_UTR_variant	1/1			A2
MAF	ENST00000569649.1	c.1118+4357del		intron_variant		5		P4

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9637 AN: 151942 Hom.: 428 Cov.: 31

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.0690

GnomAD3 exomes AF: 0.0793 AC: 12470 AN: 157210 Hom.: 662 AF XY: 0.0843 AC XY: 6975 AN XY: 82740

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.0370

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.00185

Gnomad SAS exome AF: 0.110

Gnomad FIN exome AF: 0.0990

Gnomad NFE exome AF: 0.0925

Gnomad OTH exome AF: 0.0904

GnomAD4 exome AF: 0.0826 AC: 113856 AN: 1377644 Hom.: 5157 Cov.: 26 AF XY: 0.0836 AC XY: 56886 AN XY: 680774

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.0392

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.00107

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.0968

Gnomad4 NFE exome AF: 0.0844

Gnomad4 OTH exome AF: 0.0832

GnomAD4 genome AF: 0.0633 AC: 9630 AN: 152060 Hom.: 428 Cov.: 31 AF XY: 0.0630 AC XY: 4684 AN XY: 74296

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.0457

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0964

Gnomad4 NFE AF: 0.0891

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0603 Hom.: 107

Bravo AF: 0.0555

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs148849596; hg19: chr16-79628324; COSMIC: COSV58153029;