chr16-79594639-ATT-A

Variant names:

• chr16-79594639-ATT-A
• rs66467731
• NM_005360.5:c.1119-88_1119-87delAA

Variant summary

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

The NM_005360.5(MAF):​c.1119-88_1119-87delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,197,854 control chromosomes in the GnomAD database, including 139 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (76 hom., cov: 0)
  • Exomes 𝑓: 0.027 (63 hom.)
• Consequence: MAF NM_005360.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.32
• Publications: 7 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 16-79594639-ATT-A is Benign according to our data. Variant chr16-79594639-ATT-A is described in ClinVar as [Benign]. Clinvar id is 1288364.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.1119-88_1119-87delAA		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.1119-88_1119-87delAA		intron_variant	Intron 1 of 1	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000393350.1	c.*4140_*4141delAA		3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000377019.1
MAF	ENST00000569649.1	c.1118+4144_1118+4145delAA		intron_variant	Intron 1 of 1	5		ENSP00000455097.1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2856 AN: 146946 Hom.: 76 Cov.: 0

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00770

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.000397

Gnomad SAS AF: 0.000642

Gnomad FIN AF: 0.00316

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00139

Gnomad OTH AF: 0.00988

GnomAD4 exome AF: 0.0271 AC: 28529 AN: 1050850 Hom.: 63 AF XY: 0.0281 AC XY: 14499 AN XY: 516164

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

African (AFR) AF: 0.0836 AC: 2126 AN: 25416

American (AMR) AF: 0.0320 AC: 824 AN: 25734

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 738 AN: 17906

East Asian (EAS) AF: 0.0166 AC: 485 AN: 29248

South Asian (SAS) AF: 0.0385 AC: 2099 AN: 54554

European-Finnish (FIN) AF: 0.0507 AC: 1657 AN: 32696

Middle Eastern (MID) AF: 0.0333 AC: 141 AN: 4240

European-Non Finnish (NFE) AF: 0.0233 AC: 19059 AN: 817580

Other (OTH) AF: 0.0322 AC: 1400 AN: 43476

⚠️ 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: 0.0194 AC: 2858 AN: 147004 Hom.: 76 Cov.: 0 AF XY: 0.0193 AC XY: 1375 AN XY: 71358

African (AFR) AF: 0.0646 AC: 2596 AN: 40156

American (AMR) AF: 0.00762 AC: 113 AN: 14820

Ashkenazi Jewish (ASJ) AF: 0.000291 AC: 1 AN: 3440

East Asian (EAS) AF: 0.000398 AC: 2 AN: 5020

South Asian (SAS) AF: 0.000430 AC: 2 AN: 4646

European-Finnish (FIN) AF: 0.00316 AC: 28 AN: 8874

Middle Eastern (MID) AF: 0.0104 AC: 3 AN: 288

European-Non Finnish (NFE) AF: 0.00139 AC: 93 AN: 66812

Other (OTH) AF: 0.00981 AC: 20 AN: 2038

Alfa AF: 0.000240 Hom.: 1119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 16, 2019

GeneDx

Significance: 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		1.3
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: rs66467731; hg19: chr16-79628536;