16-79600682-A-C

Variant names:

• chr16-79600682-A-C
• rs2288066
• NM_005360.5:c.-780T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005360.5(MAF):​c.-780T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 195,718 control chromosomes in the GnomAD database, including 1,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1309 hom., cov: 29)
  • Exomes 𝑓: 0.14 (668 hom.)
• Consequence: MAF NM_005360.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.203
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 16-79600682-A-C is Benign according to our data. Variant chr16-79600682-A-C is described in ClinVar as Benign. ClinVar VariationId is 1251859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.-780T>G		5_prime_UTR_variant	Exon 1 of 2	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.-780T>G		5_prime_UTR_variant	Exon 1 of 2	1	NM_005360.5	ENSP00000327048.4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16547 AN: 151534 Hom.: 1305 Cov.: 29

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0831

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.145 AC: 6384 AN: 44066 Hom.: 668 Cov.: 0 AF XY: 0.148 AC XY: 3037 AN XY: 20544

African (AFR) AF: 0.0251 AC: 24 AN: 958

American (AMR) AF: 0.171 AC: 114 AN: 666

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 299 AN: 1842

East Asian (EAS) AF: 0.378 AC: 2260 AN: 5972

South Asian (SAS) AF: 0.145 AC: 35 AN: 242

European-Finnish (FIN) AF: 0.0869 AC: 1282 AN: 14748

Middle Eastern (MID) AF: 0.0842 AC: 17 AN: 202

European-Non Finnish (NFE) AF: 0.119 AC: 2029 AN: 17054

Other (OTH) AF: 0.136 AC: 324 AN: 2382

GnomAD4 genome AF: 0.109 AC: 16554 AN: 151652 Hom.: 1309 Cov.: 29 AF XY: 0.111 AC XY: 8230 AN XY: 74068

African (AFR) AF: 0.0279 AC: 1156 AN: 41368

American (AMR) AF: 0.179 AC: 2725 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 543 AN: 3464

East Asian (EAS) AF: 0.363 AC: 1825 AN: 5024

South Asian (SAS) AF: 0.164 AC: 781 AN: 4766

European-Finnish (FIN) AF: 0.0831 AC: 876 AN: 10542

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 290

European-Non Finnish (NFE) AF: 0.122 AC: 8261 AN: 67928

Other (OTH) AF: 0.109 AC: 230 AN: 2104

Alfa AF: 0.109 Hom.: 324

Bravo AF: 0.114

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		-0.20
PromoterAI		-0.010	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs2288066; hg19: chr16-79634579;