chr16-79598581-GGTGT-G

Variant names:

• chr16-79598581-GGTGT-G
• rs5818250
• NM_005360.5:c.1118+200_1118+203delACAC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005360.5(MAF):​c.1118+200_1118+203delACAC 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
• 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-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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.1118+200_1118+203delACAC		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+200_1118+203delACAC		intron_variant	Intron 1 of 1	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000393350.1	c.*196_*199delACAC		3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000377019.1
MAF	ENST00000569649.1	c.1118+200_1118+203delACAC		intron_variant	Intron 1 of 1	5		ENSP00000455097.1

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

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

African (AFR) AF: 0.0437 AC: 1280 AN: 29312

American (AMR) AF: 0.00594 AC: 174 AN: 29304

Ashkenazi Jewish (ASJ) AF: 0.00776 AC: 153 AN: 19716

East Asian (EAS) AF: 0.0204 AC: 634 AN: 31088

South Asian (SAS) AF: 0.00334 AC: 220 AN: 65958

European-Finnish (FIN) AF: 0.00302 AC: 86 AN: 28460

Middle Eastern (MID) AF: 0.00866 AC: 31 AN: 3578

European-Non Finnish (NFE) AF: 0.00273 AC: 2734 AN: 999854

Other (OTH) AF: 0.00720 AC: 377 AN: 52332

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

African (AFR) AF: 0.0412 AC: 1488 AN: 36136

American (AMR) AF: 0.00522 AC: 72 AN: 13800

Ashkenazi Jewish (ASJ) AF: 0.00150 AC: 5 AN: 3334

East Asian (EAS) AF: 0.000665 AC: 3 AN: 4514

South Asian (SAS) AF: 0.000507 AC: 2 AN: 3944

European-Finnish (FIN) AF: 0.000120 AC: 1 AN: 8338

Middle Eastern (MID) AF: 0.0185 AC: 5 AN: 270

European-Non Finnish (NFE) AF: 0.000919 AC: 59 AN: 64230

Other (OTH) AF: 0.0146 AC: 27 AN: 1854

Alfa AF: 0.00 Hom.: 370

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 31, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs5818250; hg19: chr16-79632478;