XM_024450279.2:c.*28+54874C>G

Variant names:

• chr16-79531006-G-C
• rs1895493
• XM_024450279.2:c.*28+54874C>G

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+54874C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 152,278 control chromosomes in the GnomAD database, including 547 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 0.081 (547 hom., cov: 32)
• Consequence: MAF XM_024450279.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 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: 0.0813 AC: 12369 AN: 152160 Hom.: 544 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.0813 AC: 12377 AN: 152278 Hom.: 547 Cov.: 32 AF XY: 0.0801 AC XY: 5961 AN XY: 74458

African (AFR) AF: 0.0609 AC: 2531 AN: 41564

American (AMR) AF: 0.0828 AC: 1266 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0773 AC: 268 AN: 3468

East Asian (EAS) AF: 0.0178 AC: 92 AN: 5180

South Asian (SAS) AF: 0.152 AC: 732 AN: 4818

European-Finnish (FIN) AF: 0.0515 AC: 547 AN: 10620

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0975 AC: 6628 AN: 68014

Other (OTH) AF: 0.0985 AC: 208 AN: 2112

Alfa AF: 0.0386 Hom.: 29

Bravo AF: 0.0811

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		0.44

Splicing

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

Other links and lift over

dbSNP: rs1895493; hg19: chr16-79564903;