16-79598601-T-TGTGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005360.5(MAF):c.1118+183_1118+184insGCAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,482,918 control chromosomes in the GnomAD database, including 215 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (53 hom., cov: 25)
  • Exomes 𝑓: 0.028 (162 hom.)
• Consequence: MAF NM_005360.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.31

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 16-79598601-T-TGTGC is Benign according to our data. Variant chr16-79598601-T-TGTGC is described in ClinVar as [Likely_benign]. Clinvar id is 1202104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0219 (3150/143796) while in subpopulation AMR AF= 0.0307 (434/14156). AF 95% confidence interval is 0.0283. There are 53 homozygotes in gnomad4. There are 1532 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High AC in GnomAd at 3153 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAF	NM_005360.5	c.1118+183_1118+184insGCAC		intron_variant		ENST00000326043.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAF	ENST00000326043.5	c.1118+183_1118+184insGCAC		intron_variant		1	NM_005360.5	A2
MAF	ENST00000393350.1	c.*179_*180insGCAC		3_prime_UTR_variant	1/1			A2
MAF	ENST00000569649.1	c.1118+183_1118+184insGCAC		intron_variant		5		P4

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3153 AN: 143708 Hom.: 53 Cov.: 25

Gnomad AFR AF: 0.00531

Gnomad AMI AF: 0.00558

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.000207

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0360

Gnomad MID AF: 0.0422

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0259

GnomAD4 exome AF: 0.0276 AC: 36914 AN: 1339122 Hom.: 162 Cov.: 56 AF XY: 0.0273 AC XY: 17866 AN XY: 655278

Gnomad4 AFR exome AF: 0.00460

Gnomad4 AMR exome AF: 0.0183

Gnomad4 ASJ exome AF: 0.0607

Gnomad4 EAS exome AF: 0.0000853

Gnomad4 SAS exome AF: 0.0191

Gnomad4 FIN exome AF: 0.0248

Gnomad4 NFE exome AF: 0.0294

Gnomad4 OTH exome AF: 0.0278

GnomAD4 genome AF: 0.0219 AC: 3150 AN: 143796 Hom.: 53 Cov.: 25 AF XY: 0.0220 AC XY: 1532 AN XY: 69678

Gnomad4 AFR AF: 0.00530

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.000208

Gnomad4 SAS AF: 0.0225

Gnomad4 FIN AF: 0.0360

Gnomad4 NFE AF: 0.0272

Gnomad4 OTH AF: 0.0257

Alfa AF: 0.00668 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 02, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs777759060; hg19: chr16-79632498;