chr16-79594284-T-C

Variant names:

• chr16-79594284-T-C
• rs2287974
• NM_005360.5:c.*176A>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.*176A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 649,808 control chromosomes in the GnomAD database, including 43,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9012 hom., cov: 31)
  • Exomes 𝑓: 0.37 (34894 hom.)
• Consequence: MAF NM_005360.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.01
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-79594284-T-C is Benign according to our data. Variant chr16-79594284-T-C is described in ClinVar as [Benign]. Clinvar id is 1263394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.*176A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.*176A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000569649.1	c.1118+4501A>G		intron_variant	Intron 1 of 1	5		ENSP00000455097.1
MAF	ENST00000393350.1	c.*4497A>G		downstream_gene_variant		6		ENSP00000377019.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51326 AN: 151898 Hom.: 9004 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.369 AC: 183616 AN: 497794 Hom.: 34894 Cov.: 6 AF XY: 0.367 AC XY: 97202 AN XY: 264544

African (AFR) AF: 0.242 AC: 3311 AN: 13690

American (AMR) AF: 0.308 AC: 7779 AN: 25296

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 6187 AN: 15498

East Asian (EAS) AF: 0.434 AC: 13155 AN: 30292

South Asian (SAS) AF: 0.329 AC: 16017 AN: 48708

European-Finnish (FIN) AF: 0.395 AC: 10912 AN: 27614

Middle Eastern (MID) AF: 0.410 AC: 855 AN: 2086

European-Non Finnish (NFE) AF: 0.376 AC: 115328 AN: 307108

Other (OTH) AF: 0.366 AC: 10072 AN: 27502

GnomAD4 genome AF: 0.338 AC: 51354 AN: 152014 Hom.: 9012 Cov.: 31 AF XY: 0.342 AC XY: 25374 AN XY: 74278

African (AFR) AF: 0.251 AC: 10405 AN: 41468

American (AMR) AF: 0.347 AC: 5303 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1342 AN: 3466

East Asian (EAS) AF: 0.439 AC: 2272 AN: 5174

South Asian (SAS) AF: 0.322 AC: 1546 AN: 4798

European-Finnish (FIN) AF: 0.398 AC: 4193 AN: 10540

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25189 AN: 67968

Other (OTH) AF: 0.344 AC: 728 AN: 2114

Alfa AF: 0.355 Hom.: 22187

Bravo AF: 0.332

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.51
PhyloP100		-2.0
Mutation Taster		=100/0	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: rs2287974; hg19: chr16-79628181;