XM_024450279.2:c.*28+69050G>T

Variant names:

• chr16-79516830-C-A
• rs2549513
• XM_024450279.2:c.*28+69050G>T

Variant summary

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

The XM_024450279.2(MAF):​c.*28+69050G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 152,170 control chromosomes in the GnomAD database, including 53,563 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 0.84 (53563 hom., cov: 32)
• Consequence: MAF XM_024450279.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 16 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	XM_024450279.2	c.*28+69050G>T		intron_variant	Intron 2 of 2		XP_024306047.1
MAF	XR_001751902.3	n.2015+69050G>T		intron_variant	Intron 2 of 3
MAF	XR_002957802.2	n.2015+69050G>T		intron_variant	Intron 2 of 3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127249 AN: 152052 Hom.: 53525 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.848

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

GnomAD4 genome AF: 0.837 AC: 127341 AN: 152170 Hom.: 53563 Cov.: 32 AF XY: 0.838 AC XY: 62378 AN XY: 74412

African (AFR) AF: 0.746 AC: 30950 AN: 41502

American (AMR) AF: 0.894 AC: 13675 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2969 AN: 3472

East Asian (EAS) AF: 0.920 AC: 4749 AN: 5162

South Asian (SAS) AF: 0.865 AC: 4167 AN: 4820

European-Finnish (FIN) AF: 0.861 AC: 9131 AN: 10604

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58820 AN: 67996

Other (OTH) AF: 0.850 AC: 1797 AN: 2114

Alfa AF: 0.857 Hom.: 168324

Bravo AF: 0.838

Asia WGS AF: 0.899 AC: 3128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.84
DANN	Benign	0.52
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs2549513; hg19: chr16-79550727;