16-79599908-TGCCGCCGCCGCCGCC-TGCCGCC

Variant names:

• chr16-79599908-TGCCGCCGCC-T
• rs5818251
• NM_005360.5:c.-15_-7delGGCGGCGGC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_005360.5(MAF):​c.-15_-7delGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,554,512 control chromosomes in the GnomAD database, including 52 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (26 hom., cov: 0)
  • Exomes 𝑓: 0.0013 (26 hom.)
• Consequence: MAF NM_005360.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.29
• Publications: 3 publications found

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]

MAF Gene-Disease associations (from GenCC):

• Ayme-Gripp syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• cataract 21 multiple types

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
• cataract - microcornea syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cerulean cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pulverulent cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fine-Lubinsky syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000278058 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 16-79599908-TGCCGCCGCC-T is Benign according to our data. Variant chr16-79599908-TGCCGCCGCC-T is described in ClinVar as Benign. ClinVar VariationId is 259751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0106 (1598/150802) while in subpopulation AFR AF = 0.0363 (1495/41170). AF 95% confidence interval is 0.0348. There are 26 homozygotes in GnomAd4. There are 761 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005360.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	NM_005360.5	MANE Select	c.-15_-7delGGCGGCGGC		5_prime_UTR	Exon 1 of 2	NP_005351.2
	MAF	NM_001031804.3		c.-15_-7delGGCGGCGGC		5_prime_UTR	Exon 1 of 1	NP_001026974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	ENST00000326043.5	TSL:1 MANE Select	c.-15_-7delGGCGGCGGC		5_prime_UTR	Exon 1 of 2	ENSP00000327048.4
	ENSG00000278058	ENST00000767269.1		n.41_49delCGCCGCCGC		non_coding_transcript_exon	Exon 1 of 3
	MAF	ENST00000393350.1	TSL:6	c.-15_-7delGGCGGCGGC		5_prime_UTR	Exon 1 of 1	ENSP00000377019.1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1592 AN: 150700 Hom.: 26 Cov.: 0

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00362

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000201

Gnomad SAS AF: 0.000837

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000341

Gnomad OTH AF: 0.00628

GnomAD2 exomes AF: 0.00290 AC: 568 AN: 195638 AF XY: 0.00233

Gnomad AFR exome AF: 0.0416

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.00251

Gnomad EAS exome AF: 0.000356

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000506

Gnomad OTH exome AF: 0.000808

GnomAD4 exome AF: 0.00131 AC: 1839 AN: 1403710 Hom.: 26 AF XY: 0.00116 AC XY: 809 AN XY: 699332

African (AFR) AF: 0.0386 AC: 1247 AN: 32308

American (AMR) AF: 0.00116 AC: 50 AN: 43204

Ashkenazi Jewish (ASJ) AF: 0.00284 AC: 72 AN: 25396

East Asian (EAS) AF: 0.000213 AC: 8 AN: 37522

South Asian (SAS) AF: 0.000225 AC: 19 AN: 84542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36838

Middle Eastern (MID) AF: 0.00177 AC: 8 AN: 4528

European-Non Finnish (NFE) AF: 0.000277 AC: 299 AN: 1081138

Other (OTH) AF: 0.00234 AC: 136 AN: 58234

GnomAD4 genome AF: 0.0106 AC: 1598 AN: 150802 Hom.: 26 Cov.: 0 AF XY: 0.0103 AC XY: 761 AN XY: 73660

African (AFR) AF: 0.0363 AC: 1495 AN: 41170

American (AMR) AF: 0.00362 AC: 55 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3460

East Asian (EAS) AF: 0.000201 AC: 1 AN: 4966

South Asian (SAS) AF: 0.000838 AC: 4 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000341 AC: 23 AN: 67528

Other (OTH) AF: 0.00621 AC: 13 AN: 2092

Alfa AF: 0.00122 Hom.: 4066

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jan 22, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Aug 13, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3
Mutation Taster		=298/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs5818251; hg19: chr16-79633805;