chr16-79594284-T-C

Position:

• chr16-79594284-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MAF	NM_005360.5	c.*176A>G		3_prime_UTR_variant	2/2	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.*176A>G		3_prime_UTR_variant	2/2	1	NM_005360.5	ENSP00000327048	A2
MAF	ENST00000569649.1	c.1118+4501A>G		intron_variant		5		ENSP00000455097	P4
MAF	ENST00000393350.1			downstream_gene_variant				ENSP00000377019	A2

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

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.399

Gnomad4 EAS exome AF: 0.434

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.366

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

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.344

Alfa AF: 0.365 Hom.: 11451

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2287974; hg19: chr16-79628181;