16-79246401-C-T

Variant names:

• chr16-79246401-C-T
• rs9922579
• XM_024450279.2:c.*29-33500G>A

Variant summary

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

The XM_024450279.2(MAF):​c.*29-33500G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 151,952 control chromosomes in the GnomAD database, including 2,266 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 0.14 (2266 hom., cov: 30)
• Consequence: MAF XM_024450279.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	XM_024450279.2	c.*29-33500G>A		intron_variant	Intron 2 of 2		XP_024306047.1
MAF	XR_001751902.3	n.2016-33500G>A		intron_variant	Intron 2 of 3
MAF	XR_002957802.2	n.2016-33500G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21315 AN: 151834 Hom.: 2261 Cov.: 30

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0754

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.0546

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0779

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.140 AC: 21344 AN: 151952 Hom.: 2266 Cov.: 30 AF XY: 0.140 AC XY: 10371 AN XY: 74262

African (AFR) AF: 0.296 AC: 12263 AN: 41382

American (AMR) AF: 0.0754 AC: 1151 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3470

East Asian (EAS) AF: 0.0412 AC: 213 AN: 5164

South Asian (SAS) AF: 0.0544 AC: 262 AN: 4816

European-Finnish (FIN) AF: 0.146 AC: 1542 AN: 10556

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0779 AC: 5297 AN: 67978

Other (OTH) AF: 0.109 AC: 230 AN: 2114

Alfa AF: 0.0934 Hom.: 3031

Bravo AF: 0.143

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.36
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs9922579; hg19: chr16-79280298;