rs10514451

Variant names:

• chr16-79343465-A-G
• rs10514451
• XM_024450279.2:c.*29-130564T>C

Variant summary

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

The XR_001751902.3(MAF):​n.2016-130564T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,240 control chromosomes in the GnomAD database, including 350 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 0.046 (350 hom., cov: 32)
• Consequence: MAF XR_001751902.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	XM_024450279.2	c.*29-130564T>C		intron_variant	Intron 2 of 2		XP_024306047.1
MAF	XR_001751902.3	n.2016-130564T>C		intron_variant	Intron 2 of 3
MAF	XR_002957802.2	n.2016-130564T>C		intron_variant	Intron 2 of 3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7052 AN: 152122 Hom.: 351 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0464 AC: 7061 AN: 152240 Hom.: 350 Cov.: 32 AF XY: 0.0445 AC XY: 3311 AN XY: 74428

African (AFR) AF: 0.130 AC: 5384 AN: 41512

American (AMR) AF: 0.0251 AC: 384 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3470

East Asian (EAS) AF: 0.0153 AC: 79 AN: 5178

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4818

European-Finnish (FIN) AF: 0.00612 AC: 65 AN: 10628

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0136 AC: 926 AN: 68024

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0268 Hom.: 187

Bravo AF: 0.0516

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0080
DANN	Benign	0.50
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs10514451; hg19: chr16-79377362;