chr16-79594241-C-G

Variant names:

• chr16-79594241-C-G
• rs78847445
• NM_005360.5:c.*219G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005360.5(MAF):​c.*219G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 547,698 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (18 hom.)
• Consequence: MAF NM_005360.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.635
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-79594241-C-G is Benign according to our data. Variant chr16-79594241-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1193568.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1679/152250) while in subpopulation AFR AF = 0.0383 (1591/41542). AF 95% confidence interval is 0.0367. There are 27 homozygotes in GnomAd4. There are 804 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.*219G>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.*219G>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000569649.1	c.1118+4544G>C		intron_variant	Intron 1 of 1	5		ENSP00000455097.1
MAF	ENST00000393350.1	c.*4540G>C		downstream_gene_variant		6		ENSP00000377019.1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1679 AN: 152132 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0384

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00718

GnomAD4 exome AF: 0.00161 AC: 636 AN: 395448 Hom.: 18 Cov.: 3 AF XY: 0.00128 AC XY: 269 AN XY: 209872

African (AFR) AF: 0.0397 AC: 462 AN: 11636

American (AMR) AF: 0.00286 AC: 51 AN: 17854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12388

East Asian (EAS) AF: 0.00 AC: 0 AN: 27218

South Asian (SAS) AF: 0.0000723 AC: 3 AN: 41506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20618

Middle Eastern (MID) AF: 0.000579 AC: 1 AN: 1726

European-Non Finnish (NFE) AF: 0.000167 AC: 40 AN: 239430

Other (OTH) AF: 0.00342 AC: 79 AN: 23072

GnomAD4 genome AF: 0.0110 AC: 1679 AN: 152250 Hom.: 27 Cov.: 33 AF XY: 0.0108 AC XY: 804 AN XY: 74432

African (AFR) AF: 0.0383 AC: 1591 AN: 41542

American (AMR) AF: 0.00425 AC: 65 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68016

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.000141 Hom.: 0

Bravo AF: 0.0127

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 20, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.11
DANN	Benign	0.48
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs78847445; hg19: chr16-79628138;