16-79277512-A-G

Variant names:

• chr16-79277512-A-G
• rs4888943
• XM_024450279.2:c.*29-64611T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_024450279.2(MAF):​c.*29-64611T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,136 control chromosomes in the GnomAD database, including 49,261 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (49261 hom., cov: 32)
• Consequence: MAF XM_024450279.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121756 AN: 152018 Hom.: 49248 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.822

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.801 AC: 121809 AN: 152136 Hom.: 49261 Cov.: 32 AF XY: 0.810 AC XY: 60263 AN XY: 74380

African (AFR) AF: 0.682 AC: 28263 AN: 41450

American (AMR) AF: 0.867 AC: 13251 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2736 AN: 3470

East Asian (EAS) AF: 0.988 AC: 5122 AN: 5186

South Asian (SAS) AF: 0.862 AC: 4155 AN: 4820

European-Finnish (FIN) AF: 0.920 AC: 9758 AN: 10608

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55771 AN: 67994

Other (OTH) AF: 0.821 AC: 1733 AN: 2112

Alfa AF: 0.818 Hom.: 19716

Bravo AF: 0.793

Asia WGS AF: 0.888 AC: 3083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.4
DANN	Benign	0.60
PhyloP100		0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4888943; hg19: chr16-79311409;