16-79382666-C-T

Variant names:

• chr16-79382666-C-T
• rs7192960
• XM_024450279.2:c.*29-169765G>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.*29-169765G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,112 control chromosomes in the GnomAD database, including 11,461 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 0.31 (11461 hom., cov: 33)
• Consequence: MAF XM_024450279.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 13 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	XM_024450279.2	c.*29-169765G>A		intron_variant	Intron 2 of 2		XP_024306047.1
MAF	XR_001751902.3	n.2016-169765G>A		intron_variant	Intron 2 of 3
MAF	XR_002957802.2	n.2016-169765G>A		intron_variant	Intron 2 of 3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47552 AN: 151996 Hom.: 11407 Cov.: 33

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.313 AC: 47676 AN: 152112 Hom.: 11461 Cov.: 33 AF XY: 0.312 AC XY: 23223 AN XY: 74352

African (AFR) AF: 0.679 AC: 28177 AN: 41482

American (AMR) AF: 0.220 AC: 3367 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3468

East Asian (EAS) AF: 0.264 AC: 1362 AN: 5166

South Asian (SAS) AF: 0.316 AC: 1523 AN: 4814

European-Finnish (FIN) AF: 0.191 AC: 2024 AN: 10582

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9804 AN: 68008

Other (OTH) AF: 0.262 AC: 552 AN: 2106

Alfa AF: 0.177 Hom.: 6805

Bravo AF: 0.331

Asia WGS AF: 0.349 AC: 1210 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs7192960; hg19: chr16-79416563;