16-79598581-G-GGTGTGT

Variant names:

• chr16-79598581-G-GGTGTGT
• rs5818250
• NM_005360.5:c.1118+198_1118+203dupACACAC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005360.5(MAF):​c.1118+198_1118+203dupACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (120 hom., cov: 0)
  • Exomes 𝑓: 0.025 (32 hom.)
• Consequence: MAF NM_005360.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.149
• Publications: 4 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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-79598581-G-GGTGTGT is Benign according to our data. Variant chr16-79598581-G-GGTGTGT is described in ClinVar as [Likely_benign]. Clinvar id is 1207043.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.1118+198_1118+203dupACACAC		intron_variant	Intron 1 of 1	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.1118+198_1118+203dupACACAC		intron_variant	Intron 1 of 1	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000393350.1	c.*194_*199dupACACAC		3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000377019.1
MAF	ENST00000569649.1	c.1118+198_1118+203dupACACAC		intron_variant	Intron 1 of 1	5		ENSP00000455097.1

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4484 AN: 137176 Hom.: 119 Cov.: 0

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.0138

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0327

GnomAD4 exome AF: 0.0254 AC: 32190 AN: 1268486 Hom.: 32 Cov.: 4 AF XY: 0.0270 AC XY: 16654 AN XY: 616330

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0272 AC: 801 AN: 29404

American (AMR) AF: 0.0860 AC: 2514 AN: 29228

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 472 AN: 19970

East Asian (EAS) AF: 0.124 AC: 4101 AN: 32952

South Asian (SAS) AF: 0.0828 AC: 5476 AN: 66170

European-Finnish (FIN) AF: 0.0205 AC: 585 AN: 28560

Middle Eastern (MID) AF: 0.0359 AC: 129 AN: 3590

European-Non Finnish (NFE) AF: 0.0164 AC: 16491 AN: 1005954

Other (OTH) AF: 0.0308 AC: 1621 AN: 52658

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0327 AC: 4495 AN: 137264 Hom.: 120 Cov.: 0 AF XY: 0.0362 AC XY: 2385 AN XY: 65892

African (AFR) AF: 0.0308 AC: 1112 AN: 36140

American (AMR) AF: 0.0753 AC: 1038 AN: 13794

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 74 AN: 3336

East Asian (EAS) AF: 0.134 AC: 603 AN: 4512

South Asian (SAS) AF: 0.0830 AC: 326 AN: 3930

European-Finnish (FIN) AF: 0.0216 AC: 180 AN: 8338

Middle Eastern (MID) AF: 0.0148 AC: 4 AN: 270

European-Non Finnish (NFE) AF: 0.0164 AC: 1055 AN: 64222

Other (OTH) AF: 0.0324 AC: 60 AN: 1854

Alfa AF: 0.0138 Hom.: 370

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 06, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs5818250; hg19: chr16-79632478;