16-79598581-GGTGT-G

Position:

• chr16-79598581-GGTGT-G

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+200_1118+203del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00526 in 1,396,890 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (30 hom., cov: 0)
  • Exomes 𝑓: 0.0045 (4 hom.)
• Consequence: MAF NM_005360.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.66

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 16-79598581-GGTGT-G is Benign according to our data. Variant chr16-79598581-GGTGT-G is described in ClinVar as [Likely_benign]. Clinvar id is 1196267.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1662/137288) while in subpopulation AFR AF= 0.0412 (1488/36136). AF 95% confidence interval is 0.0394. There are 30 homozygotes in gnomad4. There are 780 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1662 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAF	NM_005360.5	c.1118+200_1118+203del		intron_variant		ENST00000326043.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAF	ENST00000326043.5	c.1118+200_1118+203del		intron_variant		1	NM_005360.5	A2
MAF	ENST00000393350.1	c.*196_*199del		3_prime_UTR_variant	1/1			A2
MAF	ENST00000569649.1	c.1118+200_1118+203del		intron_variant		5		P4

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1644 AN: 137200 Hom.: 29 Cov.: 0

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00522

Gnomad ASJ AF: 0.00150

Gnomad EAS AF: 0.000663

Gnomad SAS AF: 0.000506

Gnomad FIN AF: 0.000120

Gnomad MID AF: 0.0103

Gnomad NFE AF: 0.000918

Gnomad OTH AF: 0.0147

GnomAD4 exome AF: 0.00452 AC: 5689 AN: 1259602 Hom.: 4 AF XY: 0.00451 AC XY: 2762 AN XY: 612094

Gnomad4 AFR exome AF: 0.0437

Gnomad4 AMR exome AF: 0.00594

Gnomad4 ASJ exome AF: 0.00776

Gnomad4 EAS exome AF: 0.0204

Gnomad4 SAS exome AF: 0.00334

Gnomad4 FIN exome AF: 0.00302

Gnomad4 NFE exome AF: 0.00273

Gnomad4 OTH exome AF: 0.00720

GnomAD4 genome AF: 0.0121 AC: 1662 AN: 137288 Hom.: 30 Cov.: 0 AF XY: 0.0118 AC XY: 780 AN XY: 65900

Gnomad4 AFR AF: 0.0412

Gnomad4 AMR AF: 0.00522

Gnomad4 ASJ AF: 0.00150

Gnomad4 EAS AF: 0.000665

Gnomad4 SAS AF: 0.000507

Gnomad4 FIN AF: 0.000120

Gnomad4 NFE AF: 0.000919

Gnomad4 OTH AF: 0.0146

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

Aug 31, 2019

- -

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: rs5818250; hg19: chr16-79632478;